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Kita Shunsuke

Faculty of Pharmaceutical Sciences　Molecular Pharmaceutical Sciences　Molecular and Cellular Biological SciencesAssociate Professor
Institute for Integrated Innovations　Institute for Vaccine Research and DevelopmentAssociate Professor

Researcher basic information

■ Degree
  • 博士（生命科学）, 北海道大学
■ URL
researchmap URLホームページURL■ Various IDs
Researcher number
  • 10702003
ORCID IDJ-Global ID■ Research Keywords and Fields
Research Keyword
  • Structural biology
  • X-ray crystallography
  • 電子顕微鏡
  • 蛋白質間相互作用
  • 示差走査熱量計（DSC）
  • コロナウイルス
  • ウイルス蛋白質
  • SARS-CoV-2
  • spike
  • HIV-1
  • HIV-2
  • C型レクチン
  • HLA
  • CD1
Research Field
  • Life Science, Biophysics
  • Life Science, Structural biochemistry
■ Educational Organization

Career

■ Career
Career
  • Dec. 2024 - Present
    Hokkaido University, Faculty of Pharmaceutical Sciences, 准教授, Japan
  • Nov. 2021 - Nov. 2024
    Hokkaido University, Faculty of Pharmaceutical Sciences, 助教
  • May 2015 - Oct. 2021
    Hokkaido University, Faculty of Pharmaceutical Sciences, 特任助教
  • Jan. 2013 - Apr. 2015
    Hokkaido University, Faculty of Pharmaceutical Sciences, 博士研究員
Educational Background
  • Apr. 2008 - Dec. 2012, Hokkaido University, 生命科学院, 博士後期課程
  • Apr. 2006 - Mar. 2008, Hokkaido University, 生命科学院, 博士前期課程
  • Apr. 2002 - Mar. 2006, Hokkaido University, School of Science

Research activity information

■ Awards
  • 2022, 第８回北大・部局横断シンポジウム実行委員会, ベストプレゼンテーション賞
    喜多 俊介
  • 2022, 日本生化学会北海道支部, 若手奨励賞
    喜多 俊介
  • 2015, 加藤記念バイオサイエンス振興財団, 国際交流助成
    喜多俊介
  • 2011, クラーク財団, 博士後期課程在学生海外派遣助成
    喜多俊介
  • 2011, 吉田科学技術財団, 国際研究集会派遣研究者助成
    喜多俊介
  • 2009, 日本生物物理学会北海道支部, 北海道支部例会 発表賞
    喜多俊介
■ Papers
  • Structural determination of human nucleosomes reconstituted by the ExACT platform
    Kei-ichi Okimune; Taiki Azuma; Petra Banko; Junko Haga; Genki Terashi; Ryo Morishita; Yaeta Endo; Shunsuke Kita; Daisuke Kihara; Katsumi Maenaka; Taichi E. Takasuka
    30 Jul. 2026
  • Polymerization-Induced Functional Switching of Engineered Polyhydroxyalkanoate Synthase Directs Block Copolymerization
    Kengo Yanagawa; Atsuji Kodama; Hiroya Tomita; Shunsuke Kita; Shin-ichi Hachisuka; Hiroshi Kikukawa; Susumu Uchiyama; Katsumi Maenaka; Ken’ichiro Matsumoto
    Journal of the American Chemical Society, 14 Jun. 2026
    Scientific journal
  • Measles: Why the vaccine still works after 60 years.
    Katsumi Maenaka; Shunsuke Kita; Hideo Fukuhara
    Cell host & microbe, 34, 6, 983, 985, 10 Jun. 2026, [International Magazine]
    English, Scientific journal, The measles vaccine provides lifelong protection despite high virus mutation rates. In this issue of Cell Host & Microbe, Acciani et al. demonstrate that vaccine-induced antibodies target highly conserved epitopes within the viral glycoproteins H and F, identifying a "vulnerability nexus" that ensures antigenic stability.
  • Enhanced Sampling Reveals Metastable Conformations Driving K417N-Mediated Class I Antibody Escape
    Xu Pan; Takashi Tadokoro; Taishi Onodera; Shunsuke Kita; Yoshimasa Takahashi; Katsumi Maenaka; Hisham M. Dokainish
    Journal of Chemical Information and Modeling, 10 Nov. 2025, [Peer-reviewed]
    Scientific journal
  • Molecular basis for selection and inhibition of HIV-1 escape virus by T cells and KIR2DL2+NK cells.
    Takayuki Chikata; Kimiko Kuroki; Nozomi Kuse; Anna E Kliszczak; Wayne Paes; Nanami Tomioka; Robert Parker; Aure Aflalo; Tomohiro Akahoshi; Yu Zhang; Ryoya Yamashita; Ryuma Sakata; Hiroki Kusaka; Yosuke Watanabe; Annalisa Nicastri; Haruki Matsubara; Toyoyuki Ose; Shunsuke Kita; Shinichi Oka; Hiroyuki Gatanaga; Zhansong Lin; Nicola Ternette; Persephone Borrow; Katsumi Maenaka; Masafumi Takiguchi
    Nature communications, 16, 1, 9796, 9796, 06 Nov. 2025, [Peer-reviewed], [International Magazine]
    English, Scientific journal, NK cells and CD8+ T cells both contribute to HIV-1 control. These cells not only suppress HIV-1 replication, but also select HIV-1 escape mutant viruses. Most viruses bearing T cell escape mutations are expected to remain susceptible to NK cell suppression, but their inhibition by NK cells is unclear. We investigated the role of HIV-1-specific CD8+ T cells and NK cells recognizing superimposed Pol peptides in selection and control of HIV-1 mutant virus. KIR2DL2+NK cells have an enhanced ability to recognize HIV-1-infected cells after selection of Pol mutant virus by PolIY11-specific HLA-C*12:02-restricted T cells. Mass spectrometry-based immunopeptidome profiling of HIV-1-infected cells and analysis of crystal structures of TCR- and KIR2DL2-HLA-C*12:02-peptide complexes demonstrate the molecular basis for selection and recognition of the escape mutant epitope by TCR and KIR2DL2. The present study elucidates the mechanism for selection and inhibition of an HIV-1 escape virus by T cells and NK cells.
  • The effect of guide RNA thermal denaturation on the quality of Cas9 ribonucleoprotein-loaded lipid nanoparticle formulations
    Rina Shimizu; Yuji Kashiwakura; Morisada Hayakawa; Shunsuke Kita; Mina Sato; Masatoshi Maeki; Manabu Tokeshi; Katsumi Maenaka; Tsukasa Ohmori; Yuma Yamada; Hideyoshi Harashima; Yusuke Sato
    RSC PHARMACEUTICS, 27 Oct. 2025, [Peer-reviewed]
    English, Scientific journal
  • Thermoresponsive hydrogelation of N-acetyl chitohexaose: Gelation mechanism and application in controlled protein release
    Hiroyuki Kono; Yuya Nagaoka; Ayumu Izutsu; Shunsuke Kita; Katsumi Maenaka; Shunsuke Nishio; Takeshi Hattori; Yuka Yoshikawa; Kousuke Michishita; Taichi Usui; Takuya Isono; Makoto Ogata
    Carbohydrate Polymers, 366, 123897, 123897, Elsevier BV, Oct. 2025, [Peer-reviewed]
    Scientific journal
  • Examining the Impact of Storage Conditions on the Stability of a Liquid Formulation of mRNA-Loaded Lipid Nanoparticles.
    Mina Sato; Eleni Samaridou; Moritz Beck-Broichsitter; Masatoshi Maeki; Shunsuke Kita; Manabu Tokeshi; Katsumi Maenaka; Hideyoshi Harashima; Yusuke Sato
    Pharmaceutics, 17, 9, 14 Sep. 2025, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Background/Objectives: This study investigated the effect of storage conditions on mRNA-LNPs in situ via identification of the formulation traits necessary for improving storage stability. Methods: We synthesized an ionizable lipid, namely TOT-28, which has a hydrolysis-susceptible ester bond in its hydrophilic head group that allows it to act as an indicator of the hydrophilic environment within the mRNA-LNPs. LNPs were stored either at 4 or 25 °C for up to 8 weeks to investigate the effect of pH and temperature on ester hydrolysis, internal mRNA integrity, physicochemical properties of the LNPs, and mRNA gene expression. Results: The results indicate that, at 25 °C, a lower buffer pH increases ester hydrolysis, whereas an opposite trend slightly occurs in ester hydrolysis with storage at 4 °C. We also found that TOT-28-based LNPs were less hydrated and microviscosity was higher at 4 °C compared with storage temperature at 25 °C. Therefore, TOT-28-based LNPs seem less sensitive to external buffer solutions because of a higher-order structure when stored at lower temperatures. In addition, we found that LNPs with different ionizable lipid structures exhibit distinct responses to pH changes at specific storage temperatures. Conclusions: Our findings provide novel insights into the appropriate conditions for long-term storage of the mRNA-LNPs as a liquid formulation.
  • Understanding the structure of measles virus and its implications for novel drug discovery.
    Liuan Chen; Shunsuke Kita; Hideo Fukuhara; Katsumi Maenaka
    Expert opinion on drug discovery, 1, 10, 18 Aug. 2025, [Peer-reviewed], [International Magazine]
    English, Scientific journal, INTRODUCTION: Despite having a stably effectively vaccine for decades, the Measles virus (MV) still causes periodic outbreaks given its highly contagious nature and a consistent decline in immunization coverage, which was further exacerbated during the COVID-19 pandemic, leading to reduced immunization rates. Equally concerning, there are also no approved treatments for measles. AREAS COVERED: Herein, the authors explore the current challenges of MV therapy discovery. Firstly, the article will provide an overview of the potential drug-targeted steps in the MV infection process, followed by discussion on the characteristics of existing drugs as well as the feasibility of structure-based drug discovery. Finally, the authors highlight the current progress in the field and the future opportunities for antiviral development. This article is based on a literature review including original publications, standard sources, the Protein Data Bank and clinical trials. EXPERT OPINION: First and foremost, a comprehensive structural analysis of neutralizing antibodies and RdRp inhibitors is required for efficient antiviral development. Moreover, the therapeutic prospects and current limitations for acute MV and subacute sclerosing panencephalitis (SSPE) treatments should be considered. Due to various factors including mutations, the development of broad-spectrum antivirals may minimize many of the existing barriers.
  • Structural basis of the hepatitis B virus X protein in complex with DDB1.
    Hiroki Tanaka; Joao Diogo Dias; Basile Jay; Shunsuke Kita; Mina Sasaki; Hiroyuki Takeda; Naoki Kishimoto; Shunsuke Sasaki; Shogo Misumi; Masashi Mizokami; Christine Neuveut; Takashi Sumikama; Mikihiro Shibata; Katsumi Maenaka; Shinichi Machida
    Proceedings of the National Academy of Sciences of the United States of America, 122, 24, e2421325122, 17 Jun. 2025, [Peer-reviewed], [International Magazine]
    English, Scientific journal, A cure for chronic hepatitis B requires eliminating or permanently silencing covalently closed circular DNA (cccDNA). A pivotal target of this approach is the hepatitis B virus (HBV) X protein (HBx), which is a key factor that promotes transcription from cccDNA. However, the HBx structure remains unsolved. Here, we present the cryoelectron microscopy structure of HBx in complex with DDB1, which is an essential complex for cccDNA transcription. In this structure, hydrophobic interactions within HBx were identified, and mutational analysis highlighted their importance in the HBV life cycle. Our biochemical analysis revealed that the HBx-DDB1 complex directly interacts simultaneously with NSE3, which is a component of the SMC5/6 complex, and Spindlin1. Additionally, HBx-DDB1 complex dynamics were explored via high-speed atomic force microscopy. These findings provide comprehensive insights into the structure and function of HBx in HBV replication.
  • ARNAX is an ideal adjuvant for COVID-19 vaccines to enhance antigen-specific CD4+ and CD8+ T-cell responses and neutralizing antibody induction.
    Tomomi Kawakita; Toshiki Sekiya; Yayoi Kameda; Naoki Nomura; Marumi Ohno; Chimuka Handabile; Akari Yamaya; Hideo Fukuhara; Yuki Anraku; Shunsuke Kita; Shinsuke Toba; Hirotake Tsukamoto; Tomohiro Sawa; Hiroyuki Oshiumi; Yasushi Itoh; Katsumi Maenaka; Akihiko Sato; Hirofumi Sawa; Yasuhiko Suzuki; Lorena E Brown; David C Jackson; Hiroshi Kida; Misako Matsumoto; Tsukasa Seya; Masashi Shingai
    Journal of virology, e0229024, 15 Apr. 2025, [Peer-reviewed], [International Magazine]
    English, Scientific journal, UNLABELLED: ARNAX is a synthetic nucleotide-based Toll-like receptor 3 (TLR3) ligand that specifically stimulates the TLR3/TIR domain-containing adaptor molecule 1 (TICAM-1) pathway without activating inflammatory responses. ARNAX activates cellular immunity via cross-presentation; hence, its practical application has been demonstrated in cancer immunotherapy. Given the importance of cellular immunity in virus infections, ARNAX is expected to be a more effective vaccine adjuvant for virus infections than alum, an adjuvant approved for human use that mainly enhances humoral immunity. In the present study, the trimeric recombinant spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was prepared as a vaccine antigen and formulated with ARNAX. When T-cell and neutralizing antibody responses were evaluated in immunized mice, antigen formulated with ARNAX generated significantly larger numbers of antigenspecific CD4+ and CD8+ T cells, as well as higher titers of neutralizing antibodies, compared to antigen alone or antigen formulated with alum. In experiments where immunized mice were challenged with a SARS-CoV-2 mouse-adapted virus derived from the ancestral strain, immunization with antigen formulated with ARNAX reduced virus titers in the lungs at 3 days post-infection to a much greater extent than did immunization with either antigen alone or that formulated with alum. These results show that ARNAX potently enhances the levels of both cellular and humoral immunity above those seen with alum, providing significantly greater viral clearing responses. Thus, ARNAX may act as a useful adjuvant for prophylactic vaccines, particularly for viral infectious diseases. IMPORTANCE: Cellular immunity is a critical immunological defense system against virus infections. However, aluminum salts, the most widely used adjuvant for vaccines for human use, do not promote strong cellular immunity. To prepare for the next pandemic of viral origin, the development of Th1-type adjuvants with low adverse reactions that induce cellular immunity is necessary. ARNAX is a TLR3 agonist consisting of DNA-RNA hybrid nucleic acid, which is expected to be an adjuvant that induces cellular immunity. The present study using a coronavirus disease 2019 mouse model demonstrated that ARNAX potently induces cellular immunity in addition to humoral immunity with minimal induction of inflammatory cytokines. Therefore, ARNAX has the potential to be used as a potent and welltolerated adjuvant for vaccines against pandemic viruses emerging in the future.
  • Structural and virological identification of neutralizing antibody footprint provides insights into therapeutic antibody design against SARS-CoV-2 variants
    Yuki Anraku; Shunsuke Kita; Taishi Onodera; Akihiko Sato; Takashi Tadokoro; Shiori Ito; Yu Adachi; Ryutaro Kotaki; Tateki Suzuki; Jiei Sasaki; Nozomi Shiwa-Sudo; Naoko Iwata-Yoshikawa; Noriyo Nagata; Souta Kobayashi; Yasuhiro Kazuki; Mitsuo Oshimura; Takao Nomura; Michihito Sasaki; Yasuko Orba; Tadaki Suzuki; Hirofumi Sawa; Takao Hashiguchi; Hideo Fukuhara; Yoshimasa Takahashi; Katsumi Maenaka
    Communications Biology, 22 Mar. 2025, [Peer-reviewed], [Corresponding author]
    Scientific journal
  • Structural analysis reveals how tetrameric tyrosine-phosphorylated STAT1 is targeted by the rabies virus P-protein.
    Aoi Sugiyama; Miku Minami; Kaito Ugajin; Satomi Inaba-Inoue; Nana Yabuno; Yuichiro Takekawa; Sun Xiaomei; Shiho Takei; Mina Sasaki; Tomo Nomai; Xinxin Jiang; Shunsuke Kita; Katsumi Maenaka; Mika Hirose; Min Yao; Paul R Gooley; Gregory W Moseley; Yukihiko Sugita; Toyoyuki Ose
    Science signaling, 18, 878, eads2210, 18 Mar. 2025, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Signal transducer and activator of transcription (STAT) family members mediate signaling in the Janus kinase (JAK)-STAT pathway and are activated by phosphorylation at a conserved tyrosine residue, resulting in dimerization through reciprocal interactions between the phosphotyrosine and a Src homology 2 (SH2) domain. Tyrosine-phosphorylated STAT (pY-STAT) then translocates to the nucleus to induce the expression of genes encoding antiviral proteins. Although the active and functional forms of STATs are conventionally considered to be dimers, STATs can undergo higher-order oligomerization, which is implicated in regulating transcriptional activity. We present the cryo-electron microscopy (cryo-EM) structure of the tetrameric form of intact pY-STAT1 in complex with DNA, which indicates that interactions between the amino-terminal domains (NTDs) of STAT1 induce oligomerization. The tetrameric structure revealed a compact conformation with a previously uncharacterized binding interface: Two DNA-bound dimers are twofold symmetrically aligned to transform into a tandem DNA-binding model without NTD dimer separation. Moreover, biochemical analyses indicated that the rabies virus P-protein selectively targeted tetrameric pY-STAT1. Combined with data showing which regions contribute to the interaction between pY-STAT1 and the P-protein, we constructed a binding model explaining how P recognizes the pY-STAT1 tetramer. These data provide insight into how pathogenic viruses target signaling pathways that mediate the host immune response.
  • Structural basis for receptor-binding domain mobility of the spike in SARS-CoV-2 BA.2.86 and JN.1
    Hisano Yajima; Yuki Anraku; Yu Kaku; Kanako Terakado Kimura; Arnon Plianchaisuk; Kaho Okumura; Yoshiko Nakada-Nakura; Yusuke Atarashi; Takuya Hemmi; Daisuke Kuroda; Yoshimasa Takahashi; Shunsuke Kita; Jiei Sasaki; Hiromi Sumita; Keita Matsuno; Naganori Nao; Hirofumi Sawa; Keita Mizuma; Jingshu Li; Izumi Kida; Yume Mimura; Yuma Ohari; Shinya Tanaka; Masumi Tsuda; Lei Wang; Yoshikata Oda; Zannatul Ferdous; Kenji Shishido; Hiromi Mohri; Miki Iida; Takasuke Fukuhara; Tomokazu Tamura; Rigel Suzuki; Saori Suzuki; Shuhei Tsujino; Hayato Ito; Naoko Misawa; Ziyi Guo; Alfredo A. Hinay; Kaoru Usui; Wilaiporn Saikruang; Spyridon Lytras; Keiya Uriu; Ryo Yoshimura; Shusuke Kawakubo; Luca Nishumura; Yusuke Kosugi; Shigeru Fujita; Jarel Elgin M.Tolentino; Luo Chen; Lin Pan; Wenye Li; Maximilian Stanley Yo; Kio Horinaka; Mai Suganami; Mika Chiba; Kyoko Yasuda; Keiko Iida; Adam Patrick Strange; Naomi Ohsumi; Shiho Tanaka; Eiko Ogawa; Tsuki Fukuda; Rina Osujo; Kazuhisa Yoshimura; Kenji Sadamas; Mami Nagashima; Hiroyuki Asakura; Isao Yoshida; So Nakagawa; Kazuo Takayama; Rina Hashimoto; Sayaka Deguchi; Yukio Watanabe; Yoshitaka Nakata; Hiroki Futatsusako; Ayaka Sakamoto; Naoko Yasuhara; Tateki Suzuki; Yukari Nakajima; Takashi Irie; Ryoko Kawabata; Kaori Sasaki-Tabata; Terumasa Ikeda; Hesham Nasser; Ryo Shimizu; M. S. T. Monira Begum; Michael Jonathan; Yuka Mugita; Sharee Leong; Otowa Takahashi; Takamasa Ueno; Chihiro Motozono; Mako Toyoda; Akatsuki Saito; Anon Kosaka; Miki Kawano; Natsumi Matsubara; Tomoko Nishiuchi; Jiri Zahradnik; Prokopios Andrikopoulos; Miguel Padilla-Blanco; Aditi Konar; Jumpei Ito; Katsumi Maenaka; Kei Sato; Takao Hashiguchi
    Nature Communications, 15, 1, Springer Science and Business Media LLC, 07 Oct. 2024, [Peer-reviewed]
    Scientific journal
  • Virological characteristics of the SARS-CoV-2 Omicron EG.5.1 variant.
    Shuhei Tsujino; Sayaka Deguchi; Tomo Nomai; Miguel Padilla-Blanco; Arnon Plianchaisuk; Lei Wang; Mst Monira Begum; Keiya Uriu; Keita Mizuma; Naganori Nao; Isshu Kojima; Tomoya Tsubo; Jingshu Li; Yasufumi Matsumura; Miki Nagao; Yoshitaka Oda; Masumi Tsuda; Yuki Anraku; Shunsuke Kita; Hisano Yajima; Kaori Sasaki-Tabata; Ziyi Guo; Alfredo A Hinay Jr; Kumiko Yoshimatsu; Yuki Yamamoto; Tetsuharu Nagamoto; Hiroyuki Asakura; Mami Nagashima; Kenji Sadamasu; Kazuhisa Yoshimura; Hesham Nasser; Michael Jonathan; Olivia Putri; Yoonjin Kim; Luo Chen; Rigel Suzuki; Tomokazu Tamura; Katsumi Maenaka; Takashi Irie; Keita Matsuno; Shinya Tanaka; Jumpei Ito; Terumasa Ikeda; Kazuo Takayama; Jiri Zahradnik; Takao Hashiguchi; Takasuke Fukuhara; Kei Sato
    Microbiology and immunology, 68, 9, 305, 330, Sep. 2024, [Peer-reviewed], [International Magazine]
    English, Scientific journal, In middle to late 2023, a sublineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. We performed multiscale investigations, including phylogenetic analysis, epidemic dynamics modeling, infection experiments using pseudoviruses, clinical isolates, and recombinant viruses in cell cultures and experimental animals, and the use of human sera and antiviral compounds, to reveal the virological features of the newly emerging EG.5.1 variant. Our phylogenetic analysis and epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T are critical to its increased viral fitness. Experimental investigations on the growth kinetics, sensitivity to clinically available antivirals, fusogenicity, and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 are comparable to those of XBB.1.5. However, cryo-electron microscopy revealed structural differences between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible in our experimental setup. Our multiscale investigations provide knowledge for understanding the evolutionary traits of newly emerging pathogenic viruses, including EG.5.1, in the human population.
  • Virological characteristics of the SARS-CoV-2 Omicron XBB.1.5 variant.
    Tomokazu Tamura; Takashi Irie; Sayaka Deguchi; Hisano Yajima; Masumi Tsuda; Hesham Nasser; Keita Mizuma; Arnon Plianchaisuk; Saori Suzuki; Keiya Uriu; Mst Monira Begum; Ryo Shimizu; Michael Jonathan; Rigel Suzuki; Takashi Kondo; Hayato Ito; Akifumi Kamiyama; Kumiko Yoshimatsu; Maya Shofa; Rina Hashimoto; Yuki Anraku; Kanako Terakado Kimura; Shunsuke Kita; Jiei Sasaki; Kaori Sasaki-Tabata; Katsumi Maenaka; Naganori Nao; Lei Wang; Yoshitaka Oda; Terumasa Ikeda; Akatsuki Saito; Keita Matsuno; Jumpei Ito; Shinya Tanaka; Kei Sato; Takao Hashiguchi; Kazuo Takayama; Takasuke Fukuhara
    Nature communications, 15, 1, 1176, 1176, 08 Feb. 2024, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Circulation of SARS-CoV-2 Omicron XBB has resulted in the emergence of XBB.1.5, a new Variant of Interest. Our phylogenetic analysis suggests that XBB.1.5 evolved from XBB.1 by acquiring the S486P spike (S) mutation, subsequent to the acquisition of a nonsense mutation in ORF8. Neutralization assays showed similar abilities of immune escape between XBB.1.5 and XBB.1. We determine the structural basis for the interaction between human ACE2 and the S protein of XBB.1.5, showing similar overall structures between the S proteins of XBB.1 and XBB.1.5. We provide the intrinsic pathogenicity of XBB.1 and XBB.1.5 in hamsters. Importantly, we find that the ORF8 nonsense mutation of XBB.1.5 resulted in impairment of MHC suppression. In vivo experiments using recombinant viruses reveal that the XBB.1.5 mutations are involved with reduced virulence of XBB.1.5. Together, our study identifies the two viral functions defined the difference between XBB.1 and XBB.1.5.
  • Rational in silico design identifies two mutations that restore UT28K SARS-CoV-2 monoclonal antibody activity against Omicron BA.1.
    Tatsuhiko Ozawa; Yoshiki Ikeda; Liuan Chen; Rigel Suzuki; Atsushi Hoshino; Akira Noguchi; Shunsuke Kita; Yuki Anraku; Emiko Igarashi; Yumiko Saga; Noriko Inasaki; Shunta Taminishi; Jiei Sasaki; Yuhei Kirita; Hideo Fukuhara; Katsumi Maenaka; Takao Hashiguchi; Takasuke Fukuhara; Kenichi Hirabayashi; Hideki Tani; Hiroyuki Kishi; Hideki Niimi
    Structure (London, England : 1993), Elsevier BV, 05 Jan. 2024, [Peer-reviewed], [International Magazine]
    English, Scientific journal, SARS-CoV-2 rapidly mutates and acquires resistance to neutralizing antibodies. We report an in-silico-designed antibody that restores the neutralizing activity of a neutralizing antibody. Our previously generated antibody, UT28K, exhibited broad neutralizing activity against mutant variants; however, its efficacy against Omicron BA.1 was compromised by the mutation. Using previously determined structural information, we designed a modified-UT28K (VH T28R/N57D), UT28K-RD targeting the mutation site. In vitro and in vivo experiments demonstrated the efficacy of UT28K-RD in neutralizing Omicron BA.1. Although the experimentally determined structure partially differed from the predicted model, our study serves as a successful case of antibody design, wherein the predicted amino acid substitution enhanced the recognition of the previously elusive Omicron BA.1. We anticipate that numerous similar cases will be reported, showcasing the potential of this approach for improving protein-protein interactions. Our findings will contribute to the development of novel therapeutic strategies for highly mutable viruses, such as SARS-CoV-2.
  • 2-thiouridine is a broad-spectrum antiviral nucleoside analogue against positive-strand RNA viruses.
    Kentaro Uemura; Haruaki Nobori; Akihiko Sato; Shinsuke Toba; Shinji Kusakabe; Michihito Sasaki; Koshiro Tabata; Keita Matsuno; Naoyoshi Maeda; Shiori Ito; Mayu Tanaka; Yuki Anraku; Shunsuke Kita; Mayumi Ishii; Kayoko Kanamitsu; Yasuko Orba; Yoshiharu Matsuura; William W Hall; Hirofumi Sawa; Hiroshi Kida; Akira Matsuda; Katsumi Maenaka
    Proceedings of the National Academy of Sciences of the United States of America, 120, 42, e2304139120, 17 Oct. 2023, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are causing significant morbidity and mortality worldwide. Furthermore, over 1 million cases of newly emerging or re-emerging viral infections, specifically dengue virus (DENV), are known to occur annually. Because no virus-specific and fully effective treatments against these or many other viruses have been approved, there is an urgent need for novel, effective therapeutic agents. Here, we identified 2-thiouridine (s2U) as a broad-spectrum antiviral ribonucleoside analogue that exhibited antiviral activity against several positive-sense single-stranded RNA (ssRNA+) viruses, such as DENV, SARS-CoV-2, and its variants of concern, including the currently circulating Omicron subvariants. s2U inhibits RNA synthesis catalyzed by viral RNA-dependent RNA polymerase, thereby reducing viral RNA replication, which improved the survival rate of mice infected with DENV2 or SARS-CoV-2 in our animal models. Our findings demonstrate that s2U is a potential broad-spectrum antiviral agent not only against DENV and SARS-CoV-2 but other ssRNA+ viruses.
  • Unprecedented spike flexibility revealed by BSL3 Cryo-ET of active SARS-CoV-2 virions
    Hideo Fukuhara; Hisham M. Dokainish; Shunsuke Kita; Koshiro Tabata; Akira Takasu; Juha T. Huiskonen; Yuki Anraku; Toshiya Senda; David I. Stuart; Michihito Sasaki; Yasuko Orba; Yasuhiko Suzuki; Hirofumi Sawa; Katsumi Maenaka
    11 Oct. 2023
  • Structural delineation and computational design of SARS-CoV-2-neutralizing antibodies against Omicron subvariants.
    Saya Moriyama; Yuki Anraku; Shunta Taminishi; Yu Adachi; Daisuke Kuroda; Shunsuke Kita; Yusuke Higuchi; Yuhei Kirita; Ryutaro Kotaki; Keisuke Tonouchi; Kohei Yumoto; Tateki Suzuki; Taiyou Someya; Hideo Fukuhara; Yudai Kuroda; Tsukasa Yamamoto; Taishi Onodera; Shuetsu Fukushi; Ken Maeda; Fukumi Nakamura-Uchiyama; Takao Hashiguchi; Atsushi Hoshino; Katsumi Maenaka; Yoshimasa Takahashi
    Nature communications, 14, 1, 4198, 4198, 14 Jul. 2023, [Peer-reviewed], [International Magazine]
    English, Scientific journal, SARS-CoV-2 Omicron subvariants have evolved to evade receptor-binding site (RBS) antibodies that exist in diverse individuals as public antibody clones. We rationally selected RBS antibodies resilient to mutations in emerging Omicron subvariants. Y489 was identified as a site of virus vulnerability and a common footprint of broadly neutralizing antibodies against the subvariants. Multiple Y489-binding antibodies were encoded by public clonotypes and additionally recognized F486, potentially accounting for the emergence of Omicron subvariants harboring the F486V mutation. However, a subclass of antibodies broadly neutralized BA.4/BA.5 variants via hydrophobic binding sites of rare clonotypes along with high mutation-resilience under escape mutation screening. A computationally designed antibody based on one of the Y489-binding antibodies, NIV-10/FD03, was able to bind XBB with any 486 mutation and neutralized XBB.1.5. The structural basis for the mutation-resilience of this Y489-binding antibody group may provide important insights into the design of therapeutics resistant to viral escape.
  • Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants.
    Tomokazu Tamura; Jumpei Ito; Keiya Uriu; Jiri Zahradnik; Izumi Kida; Yuki Anraku; Hesham Nasser; Maya Shofa; Yoshitaka Oda; Spyros Lytras; Naganori Nao; Yukari Itakura; Sayaka Deguchi; Rigel Suzuki; Lei Wang; Mst Monira Begum; Shunsuke Kita; Hisano Yajima; Jiei Sasaki; Kaori Sasaki-Tabata; Ryo Shimizu; Masumi Tsuda; Yusuke Kosugi; Shigeru Fujita; Lin Pan; Daniel Sauter; Kumiko Yoshimatsu; Saori Suzuki; Hiroyuki Asakura; Mami Nagashima; Kenji Sadamasu; Kazuhisa Yoshimura; Yuki Yamamoto; Tetsuharu Nagamoto; Gideon Schreiber; Katsumi Maenaka; Takao Hashiguchi; Terumasa Ikeda; Takasuke Fukuhara; Akatsuki Saito; Shinya Tanaka; Keita Matsuno; Kazuo Takayama; Kei Sato
    Nature communications, 14, 1, 2800, 2800, 16 May 2023, [Peer-reviewed], [International Magazine]
    English, Scientific journal, In late 2022, SARS-CoV-2 Omicron subvariants have become highly diversified, and XBB is spreading rapidly around the world. Our phylogenetic analyses suggested that XBB emerged through the recombination of two cocirculating BA.2 lineages, BJ.1 and BM.1.1.1 (a progeny of BA.2.75), during the summer of 2022. XBB.1 is the variant most profoundly resistant to BA.2/5 breakthrough infection sera to date and is more fusogenic than BA.2.75. The recombination breakpoint is located in the receptor-binding domain of spike, and each region of the recombinant spike confers immune evasion and increases fusogenicity. We further provide the structural basis for the interaction between XBB.1 spike and human ACE2. Finally, the intrinsic pathogenicity of XBB.1 in male hamsters is comparable to or even lower than that of BA.2.75. Our multiscale investigation provides evidence suggesting that XBB is the first observed SARS-CoV-2 variant to increase its fitness through recombination rather than substitutions.
  • Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 variant.
    Akatsuki Saito; Tomokazu Tamura; Jiri Zahradnik; Sayaka Deguchi; Koshiro Tabata; Yuki Anraku; Izumi Kimura; Jumpei Ito; Daichi Yamasoba; Hesham Nasser; Mako Toyoda; Kayoko Nagata; Keiya Uriu; Yusuke Kosugi; Shigeru Fujita; Maya Shofa; Mst Monira Begum; Ryo Shimizu; Yoshitaka Oda; Rigel Suzuki; Hayato Ito; Naganori Nao; Lei Wang; Masumi Tsuda; Kumiko Yoshimatsu; Jin Kuramochi; Shunsuke Kita; Kaori Sasaki-Tabata; Hideo Fukuhara; Katsumi Maenaka; Yuki Yamamoto; Tetsuharu Nagamoto; Hiroyuki Asakura; Mami Nagashima; Kenji Sadamasu; Kazuhisa Yoshimura; Takamasa Ueno; Gideon Schreiber; Akifumi Takaori-Kondo; Kotaro Shirakawa; Hirofumi Sawa; Takashi Irie; Takao Hashiguchi; Kazuo Takayama; Keita Matsuno; Shinya Tanaka; Terumasa Ikeda; Takasuke Fukuhara; Kei Sato
    Cell host & microbe, 30, 11, 1540, 1555, 09 Nov. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, The SARS-CoV-2 Omicron BA.2.75 variant emerged in May 2022. BA.2.75 is a BA.2 descendant but is phylogenetically distinct from BA.5, the currently predominant BA.2 descendant. Here, we show that BA.2.75 has a greater effective reproduction number and different immunogenicity profile than BA.5. We determined the sensitivity of BA.2.75 to vaccinee and convalescent sera as well as a panel of clinically available antiviral drugs and antibodies. Antiviral drugs largely retained potency, but antibody sensitivity varied depending on several key BA.2.75-specific substitutions. The BA.2.75 spike exhibited a profoundly higher affinity for its human receptor, ACE2. Additionally, the fusogenicity, growth efficiency in human alveolar epithelial cells, and intrinsic pathogenicity in hamsters of BA.2.75 were greater than those of BA.2. Our multilevel investigations suggest that BA.2.75 acquired virological properties independent of BA.5, and the potential risk of BA.2.75 to global health is greater than that of BA.5.
  • Structure of the human galanin receptor 2 bound to galanin and Gq reveals the basis of ligand specificity and how binding affects the G-protein interface.
    Yunseok Heo; Naito Ishimoto; Ye-Eun Jeon; Ji-Hye Yun; Mio Ohki; Yuki Anraku; Mina Sasaki; Shunsuke Kita; Hideo Fukuhara; Tatsuya Ikuta; Kouki Kawakami; Asuka Inoue; Katsumi Maenaka; Jeremy R H Tame; Weontae Lee; Sam-Yong Park
    PLoS biology, 20, 8, e3001714, Aug. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Galanin is a neuropeptide expressed in the central and peripheral nervous systems, where it regulates various processes including neuroendocrine release, cognition, and nerve regeneration. Three G-protein coupled receptors (GPCRs) for galanin have been discovered, which is the focus of efforts to treat diseases including Alzheimer's disease, anxiety, and addiction. To understand the basis of the ligand preferences of the receptors and to assist structure-based drug design, we used cryo-electron microscopy (cryo-EM) to solve the molecular structure of GALR2 bound to galanin and a cognate heterotrimeric G-protein, providing a molecular view of the neuropeptide binding site. Mutant proteins were assayed to help reveal the basis of ligand specificity, and structural comparison between the activated GALR2 and inactive hβ2AR was used to relate galanin binding to the movements of transmembrane (TM) helices and the G-protein interface.
  • Novel super-neutralizing antibody UT28K is capable of protecting against infection from a wide variety of SARS-CoV-2 variants.
    Tatsuhiko Ozawa; Hideki Tani; Yuki Anraku; Shunsuke Kita; Emiko Igarashi; Yumiko Saga; Noriko Inasaki; Hitoshi Kawasuji; Hiroshi Yamada; So-Ichiro Sasaki; Mayu Somekawa; Jiei Sasaki; Yoshihiro Hayakawa; Yoshihiro Yamamoto; Yoshitomo Morinaga; Nobuyuki Kurosawa; Masaharu Isobe; Hideo Fukuhara; Katsumi Maenaka; Takao Hashiguchi; Hiroyuki Kishi; Isao Kitajima; Shigeru Saito; Hideki Niimi
    mAbs, 14, 1, 2022, [Peer-reviewed]
    Scientific journal
  • A SARS-CoV-2 antibody broadly neutralizes SARS-related coronaviruses and variants by coordinated recognition of a virus-vulnerable site.
    Taishi Onodera; Shunsuke Kita; Yu Adachi; Saya Moriyama; Akihiko Sato; Takao Nomura; Shuhei Sakakibara; Takeshi Inoue; Takashi Tadokoro; Yuki Anraku; Kohei Yumoto; Cong Tian; Hideo Fukuhara; Michihito Sasaki; Yasuko Orba; Nozomi Shiwa; Naoko Iwata; Noriyo Nagata; Tateki Suzuki; Jiei Sasaki; Tsuyoshi Sekizuka; Keisuke Tonouchi; Lin Sun; Shuetsu Fukushi; Hiroyuki Satofuka; Yasuhiro Kazuki; Mitsuo Oshimura; Tomohiro Kurosaki; Makoto Kuroda; Yoshiharu Matsuura; Tadaki Suzuki; Hirofumi Sawa; Takao Hashiguchi; Katsumi Maenaka; Yoshimasa Takahashi
    Immunity, 54, 10, 2385, 2398, 24 Aug. 2021, [Peer-reviewed], [Lead author], [International Magazine]
    English, Scientific journal, Potent neutralizing SARS-CoV-2 antibodies often target the spike protein receptor-binding site (RBS), but the variability of RBS epitopes hampers broad neutralization of multiple sarbecoviruses and drifted viruses. Here, using humanized mice, we identified an RBS antibody with a germline VH gene that potently neutralized SARS-related coronaviruses, including SARS-CoV and SARS-CoV-2 variants. X-ray crystallography revealed coordinated recognition by the heavy chain of non-RBS conserved sites and the light chain of RBS with a binding angle mimicking the angiotensin-converting enzyme 2 (ACE2) receptor. The minimum footprints in the hypervariable region of RBS contributed to the breadth of neutralization, which was enhanced by immunoglobulin G3 (IgG3) class switching. The coordinated binding resulted in broad neutralization of SARS-CoV and emerging SARS-CoV-2 variants of concern. Low-dose therapeutic antibody treatment in hamsters reduced the virus titers and morbidity during SARS-CoV-2 challenge. The structural basis for broad neutralizing activity may inform the design of a broad spectrum of therapeutics and vaccines.
  • Structure, solubility, and permeability relationships in a diverse middle molecule library.
    Hiroyuki Miyachi; Kayoko Kanamitsu; Mayumi Ishii; Eri Watanabe; Akira Katsuyama; Satoko Otsuguro; Fumika Yakushiji; Mizuki Watanabe; Kouhei Matsui; Yukina Sato; Satoshi Shuto; Takashi Tadokoro; Shunsuke Kita; Takanori Matsumaru; Akira Matsuda; Tomoyasu Hirose; Masato Iwatsuki; Yasuteru Shigeta; Tetsuo Nagano; Hirotatsu Kojima; Satoshi Ichikawa; Toshiaki Sunazuka; Katsumi Maenaka
    Bioorganic & medicinal chemistry letters, 37, 127847, 127847, 08 Feb. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, To develop methodology to predict the potential druggability of middle molecules, we examined the structure, solubility, and permeability relationships of a diverse library (HKDL ver.1) consisting of 510 molecules (359 natural product derivatives, 76 non-natural products, 46 natural products, and 29 non-natural product derivatives). The library included peptides, depsipeptides, macrolides, and lignans, and 476 of the 510 compounds had a molecular weight in the range of 500 to 2,000 Da. The solubility and passive diffusion velocity of the middle molecules were assessed using the parallel artificial membrane permeability assay (PAMPA). Quantitative values of solubility of 471 molecules and passive diffusion velocity of 287 molecules were obtained, and their correlations with the structural features of the molecules were examined. Based on the results, we propose a method to predict the passive diffusion characteristics of middle molecules from their three-dimensional structural features.
  • Efficient preparation of human and mouse CD1d proteins using silkworm baculovirus expression system.
    Hiroki Kusaka; Shunsuke Kita; Takashi Tadokoro; Kouki Yoshida; Yoshiyuki Kasai; Harumi Niiyama; Yukari Fujimoto; Shinya Hanashima; Michio Murata; Shigeru Sugiyama; Toyoyuki Ose; Kimiko Kuroki; Katsumi Maenaka
    Protein expression and purification, 172, 105631, 105631, Aug. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, CD1d is a major histocompatibility complex (MHC) class I-like glycoprotein and binds to glycolipid antigens that are recognized by natural killer T (NKT) cells. To date, our understanding of the structural basis for glycolipid binding and receptor recognition of CD1d is still limited. Here, we established a preparation method for the ectodomain of human and mouse CD1d using a silkworm-baculovirus expression system. The co-expression of human and mouse CD1d and β2-microglobulin (β2m) in the silkworm-baculovirus system was successful, but the yield of human CD1d was low. A construct of human CD1d fused with β2m via a flexible GS linker as a single polypeptide was prepared to improve protein yield. The production of this single-chained complex was higher (50 μg/larva) than that of the co-expression complex. Furthermore, differential scanning calorimetry revealed that the linker made the CD1d complex more stable and homogenous. These results suggest that the silkworm-baculovirus expression system is useful for structural and biophysical studies of CD1d in several aspects including low cost, easy handling, biohazard-free, rapid, and high yielding.
  • Structure of HIV-2 Nef Reveals Features Distinct from HIV-1 Involved in Immune Regulation.
    Kengo Hirao; Sophie Andrews; Kimiko Kuroki; Hiroki Kusaka; Takashi Tadokoro; Shunsuke Kita; Toyoyuki Ose; Sarah L Rowland-Jones; Katsumi Maenaka
    iScience, 23, 1, 100758, 100758, 24 Jan. 2020, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
    English, The human immunodeficiency virus (HIV) accessory protein Nef plays a major role in establishing and maintaining infection, particularly through immune evasion. Many HIV-2-infected people experience long-term viral control and survival, resembling HIV-1 elite control. HIV-2 Nef has overlapping but also distinct functions from HIV-1 Nef. Here we report the crystal structure of HIV-2 Nef core. The di-leucine sorting motif forms a helix bound to neighboring molecules, and moreover, isothermal titration calorimetry demonstrated that the CD3 endocytosis motif can directly bind to HIV-2 Nef, ensuring AP-2-mediated endocytosis for CD3. The highly conserved C-terminal region forms a α-helix, absent from HIV-1. We further determined the structure of simian immunodeficiency virus (SIV) Nef harboring this region, demonstrating similar C-terminal α-helix, which may contribute to AP-1 binding for MHC-I downregulation. These results provide insights into the distinct pathogenesis of HIV-2 infection.
  • Structural and Functional Basis for LILRB Immune Checkpoint Receptor Recognition of HLA-G Isoforms.
    Kimiko Kuroki; Haruki Matsubara; Ryo Kanda; Naoyuki Miyashita; Mitsunori Shiroishi; Yuko Fukunaga; Jun Kamishikiryo; Atsushi Fukunaga; Hideo Fukuhara; Kaoru Hirose; Joan S Hunt; Yuji Sugita; Shunsuke Kita; Toyoyuki Ose; Katsumi Maenaka
    Journal of immunology (Baltimore, Md. : 1950), 203, 12, 3386, 3394, 15 Dec. 2019, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
    English, Scientific journal, Human leukocyte Ig-like receptors (LILR) LILRB1 and LILRB2 are immune checkpoint receptors that regulate a wide range of physiological responses by binding to diverse ligands, including HLA-G. HLA-G is exclusively expressed in the placenta, some immunoregulatory cells, and tumors and has several unique isoforms. However, the recognition of HLA-G isoforms by LILRs is poorly understood. In this study, we characterized LILR binding to the β2-microglobulin (β2m)-free HLA-G1 isoform, which is synthesized by placental trophoblast cells and tends to dimerize and multimerize. The multimerized β2m-free HLA-G1 dimer lacked detectable affinity for LILRB1, but bound strongly to LILRB2. We also determined the crystal structure of the LILRB1 and HLA-G1 complex, which adopted the typical structure of a classical HLA class I complex. LILRB1 exhibits flexible binding modes with the α3 domain, but maintains tight contacts with β2m, thus accounting for β2m-dependent binding. Notably, both LILRB1 and B2 are oriented at suitable angles to permit efficient signaling upon complex formation with HLA-G1 dimers. These structural and functional features of ligand recognition by LILRs provide novel insights into their important roles in the biological regulations.
  • Crystal structure of the complex between venom toxin and serum inhibitor from Viperidae snake.
    Narumi Shioi; Takashi Tadokoro; Seijiro Shioi; Yuki Okabe; Haruki Matsubara; Shunsuke Kita; Toyoyuki Ose; Kimiko Kuroki; Shigeyuki Terada; Katsumi Maenaka
    The Journal of biological chemistry, 294, 4, 1250, 1256, 25 Jan. 2019, [Peer-reviewed], [International Magazine]
    English, Venomous snakes have endogenous proteins that neutralize the toxicity of their venom components. We previously identified five small serum proteins (SSP-1-SSP-5) from a highly venomous snake belonging to the family Viperidae as inhibitors of various toxins from snake venom. The endogenous inhibitors belong to the prostate secretory protein of 94 amino acids (PSP94) family. SSP-2 interacts with triflin, which is a member of the cysteine-rich secretory protein (CRISP) family that blocks smooth muscle contraction. However, the structural basis for the interaction and the biological roles of these inhibitors are largely unknown. Here, we determined the crystal structure of the SSP-2-triflin complex at 2.3 Å resolution. A concave region centrally located in the N-terminal domain of triflin is fully occupied by the terminal β-strands of SSP-2. SSP-2 does not bind tightly to the C-terminal cysteine-rich domain of triflin; this domain is thought to be responsible for its channel-blocker function. Instead, the cysteine-rich domain is tilted 7.7° upon binding to SSP-2, and the inhibitor appears to sterically hinder triflin binding to calcium channels. These results help explain how an endogenous inhibitor prevents the venomous protein from maintaining homeostasis in the host. Furthermore, this interaction also sheds light on the binding interface between the human homologues PSP94 and CRISP-3, which are up-regulated in prostate and ovarian cancers.
  • X-ray crystal structure of Escherichia coli HspQ, a protein involved in the retardation of replication initiation
    Yoshito Abe; Seijiro Shioi; Shunsuke Kita; Hikaru Nakata; Katsumi Maenaka; Daisuke Kohda; Tsutomu Katayama; Tadashi Ueda
    FEBS LETTERS, 591, 22, 3805, 3816, Nov. 2017, [Peer-reviewed]
    English, Scientific journal
  • Isolated Polar Amino Acid Residues Modulate Lipid Binding in the Large Hydrophobic Cavity of CD1d
    Shinsuke Inuki; Toshihiko Aiba; Natsumi Hirata; Osamu Ichihara; Daisuke Yoshidome; Shunsuke Kita; Katsumi Maenaka; Koichi Fukase; Yukari Fujimoto
    ACS CHEMICAL BIOLOGY, 11, 11, 3132, 3139, Nov. 2016, [Peer-reviewed]
    English, Scientific journal
  • Establishment of the BacMam system using silkworm baculovirus
    Atsutoshi Imai; Takashi Tadokoro; Shunsuke Kita; Masataka Horiuchi; Hideo Fukuhara; Katsumi Maenaka
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 478, 2, 580, 585, Sep. 2016, [Peer-reviewed]
    English, Scientific journal
  • Synthesis and Th1-immunostimulatory activity of alpha-galactosylceramide analogues bearing a halogen-containing or selenium-containing acyl chain
    Md. Imran Hossain; Shinya Hanashima; Takuto Nomura; Sebastien Lethu; Hiroshi Tsuchikawa; Michio Murata; Hiroki Kusaka; Shunsuke Kita; Katsumi Maenaka
    BIOORGANIC & MEDICINAL CHEMISTRY, 24, 16, 3687, 3695, Aug. 2016, [Peer-reviewed]
    English, Scientific journal
  • Crystal structure of extracellular domain of human lectin-like transcript 1 (LLT1), the ligand for natural killer receptor-P1A
    Shunsuke Kita; Haruki Matsubara; Yoshiyuki Kasai; Takaharu Tamaoki; Yuki Okabe; Hideo Fukuhara; Jun Kamishikiryo; Elena Krayukhina; Susumu Uchiyama; Toyoyuki Ose; Kimiko Kuroki; Katsumi Maenaka
    EUROPEAN JOURNAL OF IMMUNOLOGY, 45, 6, 1605, 1613, Jun. 2015, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • Heat Shock Protein 70 Regulates Degradation of the Mumps Virus Phosphoprotein via the Ubiquitin-Proteasome Pathway
    Hiroshi Katoh; Toru Kubota; Shunsuke Kita; Yuichiro Nakatsu; Natsuko Aoki; Yoshio Mori; Katsumi Maenaka; Makoto Takeda; Minoru Kidokoro
    JOURNAL OF VIROLOGY, 89, 6, 3188, 3199, Mar. 2015, [Peer-reviewed]
    English, Scientific journal
  • Crystal structure of a putative methyltransferase SAV1081 from staphylococcus aureus
    Shunsuke Kita; Yoshikazu Tanaka; Nagisa Hirano; Satoshi Kimura; Takeo Suzuki; Tsutomu Suzuki; Min Yao; Isao Tanaka
    Protein and Peptide Letters, 20, 5, 530, 537, May 2013, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • Crystallization and preliminary X-ray crystallographic analysis of dihydrouridine synthase from Thermus thermophilus and its complex with tRNA
    Futao Yu; Yoshikazu Tanaka; Shiho Yamamoto; Akiyoshi Nakamura; Shunsuke Kita; Nagisa Hirano; Isao Tanaka; Min Yao
    ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS, 67, 685, 688, Jun. 2011, [Peer-reviewed]
    English, Scientific journal
■ Other Activities and Achievements
■ Books and other publications
  • SARS-CoV-2スパイクタンパク質と中和抗体のcryo-EM解析
    木村 香菜子, 喜多 俊介, 橋口 隆生
    ファルマシア 61 (7), Jul. 2025
  • Structure Analysis of SARS-CoV-2 Spike Protein
    喜多俊介; 染谷太陽; 野間井智; 安楽佑樹; 前仲勝実, ミニ特集
    日本結晶学会誌 66巻2号, Feb. 2025
  • 感染を制御する液性免疫 感染症に対する抗体医薬品の開発
    染谷太陽; 喜多俊介; 前仲勝実
    炎症と免疫 32(6), Oct. 2024, [Contributor]
  • SARS-CoV-2に対する中和抗体の研究
    喜多俊介
    北海道医療新聞, Jul. 2024
  • 【あなたのラボから薬を生み出す アカデミア創薬の実践 All JAPAN体制の先端技術支援を利用した創薬の最前線】(第2章)創薬標的タンパク質の構造解析と分子設計の革新的進歩 BSL3クライオ電子顕微鏡を用いた感染症創薬・ワクチン研究とその展望
    前仲 勝実; 福原 秀雄; Dokainish Hisham; 安楽 佑樹; 喜多 俊介
    実験医学 42(2) 246-252, Feb. 2024, [Contributor]
  • 医療薬学ブラッシュアップ講座 新型コロナウイルス感染症に対する抗体医薬品の開発
    喜多俊介; 前仲勝実
    道薬誌、41 (1), Jan. 2024
  • ゲルろ過クロマトグラフィーの実際
    喜多俊介
    Drug Delivery System, 3803, 2023
  • SARS-CoV-2 infection and development of neutralizing antibodies.
    安楽佑樹; 喜多俊介; 福原秀雄; 前仲勝実
    月刊臨床免疫・アレルギー科, 278巻6号、科学評論社, 2022, [Contributor]
  • 構造生命科学による創薬への挑戦 構造解析から創薬へ
    安楽 佑樹; 喜多 俊介; 前仲 勝実, タンパク質立体構造に基づいた抗ウイルス薬の創製戦略
    医学のあゆみ 278巻6号、医歯薬出版, Aug. 2021, [Contributor]
  • 膜タンパク質工学ハンドブック
    前仲 勝実; 喜多 俊介; 古川 敦; 野村 尚生; 福原 秀雄; 前田 直良, 第7章 免疫、1 免疫系表面受容体と細胞コミュニケーション
    エヌ・ティー・エス, Apr. 2020, 9784860435370, i, 5, 14, 538, 18p, 図版42p, Japanese, [Contributor]
  • Silkworm Biofactory
    Shunsuke Kita, Silkworm Expression of Cell Surface Molecules
    CRC Press, 2018, [Contributor]
  • HLAの立体構造と免疫制御受容体の分子認識機構
    前仲 勝実; 喜多 俊介; 黒木 喜美子
    日本組織適合性学会, Oct. 2016, Japanese
  • Encyclopedia of Immunobiology
    Shunsuke KKita; Maenaka Kita, Structures and Functions of MHC-like Proteins (271-278)
    Elsevier, 2016, [Contributor]
  • Advanced Methods in Structural Biology
    Kita S; Maenaka K; Tadokoro T, Expression of Proteins in Insect and Mammalian Cells (p25-45)
    Springer, 2016, [Contributor]
  • C-Type Lectin Receptors in Immunity
    Furukawa A; Kita S; Tadokoro T; Fukuhara H; Maenaka K, Structural Aspects of C-type Lectin Receptors (p179-190)
    Springer, 2016, [Contributor]
  • タンパク質結晶の最前線
    喜多俊介; 前仲勝実; 福原秀雄, 1.1 組換え発現系 (p9-17)
    シーエムシー出版, 2013, [Contributor]
■ Lectures, oral presentations, etc.
  • In silico design and structural characterization of a SARS-CoV-2 antibody
    Shunsuke Kita
    KSBMB 2026, 28 May 2026, English
  • マウス由来NKT細胞のT細胞受容体の調製と構造解析
    喜多 俊介
    日本薬学会年会第146年会, 28 Mar. 2026
  • Single particle analysis of silkworm endogenous vitellogenin
    Shunsuke Kita; Hiroki Numata; Mina Sasaki; Yuki Anraku; Katsumi Maenaka
    AsCA2025, 04 Dec. 2025, English, Oral presentation
  • Structure analysis of SARS-CoV-2 spike protein and approach to the drug discovery
    Shunsuke Kita
    The 32nd Pharma Science Forum, 09 Oct. 2025
  • Preparation of HIV-2 Env trimer and evaluation of structural features
    喜多 俊介; 安楽 佑樹; 福原 秀雄; Thushan I. de Silva; James E. Robinson; Yvonne Jones; David Stuar; Juha T Huiskonen; Sarah Rowland-Jones; 前仲 勝実
    第71回日本ウイルス学会学術集会, 04 Nov. 2024
  • 北大クライオ電子顕微鏡システムの現状と展望
    喜多 俊介
    第３１回 ファーマサイエンスフォーラム, 28 Aug. 2024
  • BINDS支援と クライオ電子顕微鏡施設の紹介
    喜多 俊介
    第３０回 ファーマサイエンスフォーラム, 13 Mar. 2024
  • 北大薬学部におけるクライオ電子顕微鏡施設の紹介
    喜多俊介
    日本顕微鏡学会 学術シンポジウム, 11 Nov. 2023, Nominated symposium
  • X線と電子顕微鏡を併用してとらえるSARS-CoV-2に対する中和抗体の分子基盤
    喜多俊介; 前仲勝実
    2023年度 日本結晶学会, 29 Oct. 2023, Nominated symposium
  • SARS-CoV-2に対する中和抗体の分子基盤
    喜多 俊介; 前仲 勝実
    第70回日本ウイルス学会学術集会, 26 Sep. 2023
  • 脂質抗原提示分子CD1の抗原認識機構
    喜多俊介
    日本生化学会 北海道支部例会, 15 Jul. 2023
  • Structural insight into SARS-CoV-2 neutralizing antibodies
    Shunsuke Kita
    日本薬学会 第143回年会, 28 Mar. 2023
  • 中分子創薬へのクライオ電子顕微鏡の応用
    喜多 俊介; 前仲 勝実
    日本薬学会 第143回年会, 26 Mar. 2023, Nominated symposium
  • 新型コロナウイルスの中和抗体に関する構造生物学研究
    喜多 俊介; 前仲 勝実
    第8回北大・部局横断シンポジウム, 28 Oct. 2022
  • MHC class I 様分子CD1dと糖脂質複合体のX線結晶構造解析
    喜多俊介; 秋田穂; 日下裕規; 田聡; 田所高志; 井貫 晋輔; 新山真由美; 杉山成; 村田道雄; 藤本ゆかり; 前仲勝実
    第22回日本蛋白質科学会年会, 10 Jun. 2022
  • 新型コロナウイルスspike蛋白質と中和抗体NT-193複合体のX線結晶構造解析
    喜多俊介; 小野寺大志; 安達悠; 森山彩野; 野村尚生; 田所高志; 安楽佑樹; 湯本航平; 田聡; 福原秀雄; 鈴木干城; 佐々木慈英; 福士秀悦; 里深博幸; 香月康宏; 押村光雄; 橋口隆生; 高橋宜聖; 前仲勝実
    令和3年度日本結晶学会, 19 Nov. 2021, Nominated symposium
  • 脂質抗原提示分子CD1dのX線結晶構造解析
    喜多 俊介; 日下 裕規; Md; Imran Hossain; 花島 慎弥; 井貫 晋輔; 田所 高志; 新山 真由美; 杉山 成; 相羽 俊彦; 尾瀬 農之; 黒木 喜美子; 深瀬 浩一; 藤本 ゆかり; 村田 道雄; 前仲 勝実
    日本生化学会 北海道支部例会, 13 Jul. 2018, Oral presentation
    [Domestic Conference]
  • Lectin-like transcript 1 (LLT1) C型レクチン様ドメインの結晶構造解析
    喜多俊介; 田所高志; 松原永季; 笠井宣征; 玉置貴晴; 岡部由紀; 日下裕規; 石山夢美; 福原秀雄; 上敷領淳; Elena Krayukhina; 内山進; 尾瀬農之; 黒木喜美子; 前仲勝実
    第88回日本生化学会大会（BMB2015）, Dec. 2015, Japanese, Oral presentation
    [Domestic Conference]
  • RNA binding study of 23S rRNA methyltransferase YcbY
    Kita S; Yao M; Tanaka I
    日本生物物理学会 北海道支部例会, Mar. 2009, Japanese, Oral presentation
    [Domestic Conference]
  • RNA binding study of 23S rRNA methyltransferase YcbY
    Shunsuke Kita; Yao Min; Isao Tanaka
    Hokkaido University - Mahidol University Joint Symposium, 2009
■ Syllabus
  • 大学院共通授業科目（一般科目）：自然科学・応用科学, 2024年, 修士課程, 大学院共通科目
  • 大学院共通授業科目（一般科目）：自然科学・応用科学, 2024年, 修士課程, 大学院共通科目
  • 先端生物科学実験法Ⅰ, 2024年, 学士課程, 薬学部
  • 生物物理化学, 2024年, 学士課程, 薬学部
  • 分析化学実習, 2024年, 学士課程, 薬学部
  • 薬剤学実習, 2024年, 学士課程, 薬学部
  • 物理化学Ⅰ, 2024年, 学士課程, 薬学部
  • 物理化学Ⅱ, 2024年, 学士課程, 薬学部
■ Affiliated academic society
  • THE BIOPHYSICAL SOCIETY OF JAPAN
  • PROTEIN SCIENCE SOCIETY OF JAPAN
  • THE CRYSTALLOGRAPHIC SOCIETY OF JAPAN
■ Research Themes
  • Elucidating the neutralizing antibody induction mechanism by HIV2 envelope glycoprotein
    Grants-in-Aid for Scientific Research
    01 Apr. 2024 - 31 Mar. 2027
    喜多 俊介
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 24K09337
  • Design of beta-barrel type transmembrane protein complex by combination of computational and experimental studies
    Grants-in-Aid for Scientific Research
    07 Oct. 2019 - 31 Mar. 2023
    田中 良和; 山下 恵太郎; 松浦 友亮; 喜多 俊介
    膜孔形成毒素は標的細胞の細胞膜に膜孔を形成する。膜孔は原子レベルで正確なナノメートルオーダーの孔（ナノポア）であり、これを利用した分子センサーが開発されている。更なる分子センサーの開発のために、目的に応じたサイズ・形状のナノポアを自在に作成できる技術が必要となる。本研究では、実験と計算科学を併用して膜孔のデザインを実現し、任意の分子特性のナノポアを作り出すことを目指す。本研究では黄色ブドウ球菌の膜孔形成毒素に着目して分子デザインを実施する。黄色ブドウ球菌の膜孔形成毒素は、2種類に分類される。1つはホモ7量体の膜孔を形成するアルファヘモリジン、もう一方は、2種類の異なるポリペプチド（LukF、Hlg2）が4分子ずつ会合してヘテロ8量体の膜孔を形成するガンマヘモリジンである。前年度までの研究において、アルファヘモリジンとガンマヘモリジンの立体構造情報に基づき、10種類以上のキメラタンパク質を設計・調製し、その分子特性を評価した。その結果、AFキメラのいくつかでは強い溶血活性が確認され、一方で、AG変異体はいずれも活性がなかった。そこで2021年度は、これらのキメラ変異体の立体構造を電子顕微鏡単粒子解析により解析し、溶血活性の有無と立体構造の相関について調査した。強い溶血活性を示すAF変異体についてはアルファヘモリジンと類似した7量体の構造を形成していることがわかった。また、溶血活性を示さないAG変異体については、AF変異体と同様に7量体を形成するものの、膜貫通領域が短いことがわかり、これが溶血活性を示さない原因であると推察された。
    Japan Society for the Promotion of Science, Fund for the Promotion of Joint International Research (Fostering Joint International Research (B)), Tohoku University, 19KK0178
  • Molecular basis for lipid presenting molecule CD1d
    Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists
    01 Apr. 2019 - 31 Mar. 2021
    Kita Shunsuke
    This study focuses on the events of antigen presentation by CD1d and activation of Natural killer T (NKT) cells, and the relationship between lipid loading on CD1d and immunoregulatory molecules. The purpose of this study is to construct the molecular basis of CD1d based on three-dimensional structure analysis and biophysical analysis such as surface plasmon resonance and differential scanning calorimetry. As the result, the X-ray crystal structure of the CD1d and αGalCer derivative complex was determined. From the structure, important knowledge for antigen recognition mechanism of CD1d was obtained. Further protein-protein interactions between CD1d and immune cell receptors were analyzed. Taken together, molecular basis of CD1d including three dimentional structure and protein-protein interaction was established and that could confer important knowledge for the application of CD1d molecule as biological therapy.
    Japan Society for the Promotion of Science, Grant-in-Aid for Early-Career Scientists, Hokkaido University, 19K16051
  • Molecular basis for lipid transfer particle, lipophorin
    Grants-in-Aid for Scientific Research
    Apr. 2017 - Mar. 2020
    Kita Shunsuke
    The lipid transportation of insects are carried out by protein complex, lipophorin. Lipophorin-mediated lipid transportation is an insect specific system and has a unique feature that lipohorin is recycled after lipid transportation. In order to reveal the lipid transportation mechanism of lipophorin, structure analysis of silkworm lipophorin was performed. Lipohorin proteins used in this study were purified from heamolymph of silkworm larvae and was observed by electron microscope. The observed lipohorin particles showed uniform-sized spherical shape. Further LTP proteins which work together with lipophorin were also prepared and observed by electron microscope. The result showed that LTP particles bended in a middle like shrimp.
    Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hokkaido University, Principal investigator, Competitive research funding, 17K15071
  • Development of novel theraputic agents targeting (pro) renin receptor
    Grants-in-Aid for Scientific Research
    Apr. 2016 - Mar. 2019
    Kanda Atsuhiro
    (Pro)renin receptor is known to regulate activations of tissue RAS and RAPS, and involved in the pathogenesis of several ocular disorders. However, its physiological functions remain unclear. The goal of this study is to develop a novel agent which can inhibit (P)RR functions, and determine its safety and efficacy in vitro and in vivo.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Competitive research funding, 16K11279
■ Academic and Social Contribution Activities/Other
Social Contribution Activities
  • クライオ電子顕微鏡で覗く ミクロの世界
    03 Aug. 2025
    Appearance
    2025北大オープンキャンパス
  • X線と電子線で コロナウイルスの秘密を解き明かす！
    07 Aug. 2023
    Appearance
    2023北大オープンキャンパス
  • クライオ電子顕微鏡を使って 新型コロナウイルスの スパイク蛋白質を見る！
    03 Jun. 2023
    Appearance
    北海道大学薬学部
    サイエンスカフェ2023
  • 新型コロナウイルスに対する創薬と北大薬学部の取り組み
    07 Aug. 2022 - 08 Aug. 2022
    Appearance
    2022北大オープンキャンパス
  • 作って、さわって、たんぱく質の結晶（けっしょう）で遊ぼう！
    27 Jan. 2019
    Appearance, Demonstrator
    特定非営利活動法人butukura
    さっぽろサイエンスフェスタ2018
  • 作って、さわって、たんぱく質の結晶（けっしょう）で遊ぼう！
    04 Mar. 2017
    Appearance, Demonstrator
    特定非営利活動法人butukura
    さっぽろサイエンスフェスタ2017
  • 作って、さわって、たんぱく質の結晶（けっしょう）で遊ぼう！
    17 Dec. 2016
    Appearance, Demonstrator
    特定非営利活動法人butukura
    さっぽろサイエンスフェスタ2016