期刊
CELL HOST & MICROBE
卷 28, 期 6, 页码 880-+出版社
CELL PRESS
DOI: 10.1016/j.chom.2020.11.001
关键词
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资金
- NIAID, NIH grant [R01 AI150560]
- NIGMS, NIH [R01 GM098859]
- Intramural Research Program of the Vaccine Research Center, NIAID, NIH
- Ministere de l'Economie et de l'Innovation du Quebec, Programme de soutien aux organismes de recherche et d'innovation
- Fondation du CHUM
- Canadian Institutes of Health Research, via the Immunity Task Force and a foundation grant
- Canada Research Chair on Retroviral Entry [RCHS0235 950-232424]
- MITACS Acceleration postdoctoral fellowship
- CIHR graduate fellowships
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) mediates viral entry into cells and is critical for vaccine development against coronavirus disease 2019 (COVID-19). Structural studies have revealed distinct conformations of S, but real-time information that connects these structures is lacking. Here we apply single-molecule fluorescence (Forster) resonance energy transfer (smFRET) imaging to observe conformational dynamics of S on virus particles. Virus-associated S dynamically samples at least four distinct conformational states. In response to human receptor angiotensin-converting enzyme 2 (hACE2), S opens sequentially into the hACE2-bound S conformation through at least one on-path intermediate. Conformational preferences observed upon exposure to convalescent plasma or antibodies suggest mechanisms of neutralization involving either competition with hACE2 for binding to the receptor-binding domain (RBD) or allosteric interference with conformational changes required for entry. Our findings inform on mechanisms of S recognition and conformations for immunogen design.
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