Structural basis for receptor-binding domain mobility of the spike in SARS-CoV-2 BA.2.86 and JN.1

機関リポジトリ (HANDLE) オープンアクセス
  • 矢島, 久乃
    Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto University
  • 安楽, 佑樹
    Laboratory of Biomolecular Science and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University
  • 郭, 悠
    Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo
  • 木村(寺角), 香菜子
    Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto University
  • Plianchaisuk, Arnon
    Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo
  • 奥村, 佳穂
    Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo; Faculty of Liberal Arts, Sophia University
  • 名倉, 淑子
    Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto University
  • 新, 勇介
    Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto University; Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases
  • 逸見, 拓矢
    Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto University
  • 黒田, 大祐
    Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases
  • 高橋, 宜聖
    Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases; Institute for Vaccine Research and Development (IVReD), Hokkaido University
  • 喜多, 俊介
    Laboratory of Biomolecular Science and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University
  • 佐々木, 慈英
    Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto University
  • 澄田, 裕美
    Research Administration Office, Institute for Life and Medical Sciences, Kyoto University
  • The Genotype to Phenotype Japan, (G2P-Japan) Consortium
  • 伊東, 潤平
    Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo; International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo
  • 前仲, 勝実
    Laboratory of Biomolecular Science and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University; Institute for Vaccine Research and Development (IVReD), Hokkaido University; Division of Pathogen Structure, International Institute for Zoonosis Control, Hokkaido University; Global Station for Biosurfaces and Drug Discovery, Hokkaido University; Kyushu University
  • 佐藤, 佳
    Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo; International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo; Graduate School of Medicine, The University of Tokyo; Graduate School of Frontier Sciences, The University of Tokyo; CREST, Japan Science and Technology Agency; International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo; Collaboration Unit for Infection, Joint Research Center for Human Retrovirus Infection, Kumamoto University; MRC-University of Glasgow Centre for Virus Research
  • 橋口, 隆生
    Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto University; CREST, Japan Science and Technology Agency; Kyoto University Immunomonitoring Center, Kyoto University

説明

Since 2019, SARS-CoV-2 has undergone mutations, resulting in pandemic and epidemic waves. The SARS-CoV-2 spike protein, crucial for cellular entry, binds to the ACE2 receptor exclusively when its receptor-binding domain (RBD) adopts the up-conformation. However, whether ACE2 also interacts with the RBD in the down-conformation to facilitate the conformational shift to RBD-up remains unclear. Herein, we present the structures of the BA.2.86 and the JN.1 spike proteins bound to ACE2. Notably, we successfully observed the ACE2-bound down-RBD, indicating an intermediate structure before the RBD-up conformation. The wider and mobile angle of RBDs in the up-state provides space for ACE2 to interact with the down-RBD, facilitating the transition to the RBD-up state. The K356T, but not N354-linked glycan, contributes to both of infectivity and neutralizing-antibody evasion in BA.2.86. These structural insights the spike-protein dynamics would help understand the mechanisms underlying SARS-CoV-2 infection and its neutralization.

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詳細情報 詳細情報について

  • CRID
    1050302459014697472
  • ISSN
    20411723
  • HANDLE
    2433/290595
  • 本文言語コード
    en
  • 資料種別
    journal article
  • データソース種別
    • IRDB

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