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Real-Time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles.
Lu, Maolin; Uchil, Pradeep D; Li, Wenwei; Zheng, Desheng; Terry, Daniel S; Gorman, Jason; Shi, Wei; Zhang, Baoshan; Zhou, Tongqing; Ding, Shilei; Gasser, Romain; Prévost, Jérémie; Beaudoin-Bussières, Guillaume; Anand, Sai Priya; Laumaea, Annemarie; Grover, Jonathan R; Liu, Lihong; Ho, David D; Mascola, John R; Finzi, Andrés; Kwong, Peter D; Blanchard, Scott C; Mothes, Walther.
  • Lu M; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA. Electronic address: maolin.lu@yale.edu.
  • Uchil PD; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.
  • Li W; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.
  • Zheng D; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.
  • Terry DS; Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Gorman J; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Shi W; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Zhang B; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Zhou T; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Ding S; Centre de Recherche du CHUM (CRCHUM), Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada.
  • Gasser R; Centre de Recherche du CHUM (CRCHUM), Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada.
  • Prévost J; Centre de Recherche du CHUM (CRCHUM), Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada.
  • Beaudoin-Bussières G; Centre de Recherche du CHUM (CRCHUM), Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada.
  • Anand SP; Centre de Recherche du CHUM (CRCHUM), Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada; Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada.
  • Laumaea A; Centre de Recherche du CHUM (CRCHUM), Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada.
  • Grover JR; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.
  • Liu L; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
  • Ho DD; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
  • Mascola JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Finzi A; Centre de Recherche du CHUM (CRCHUM), Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada; Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada.
  • Kwong PD; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Blanchard SC; Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Mothes W; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA. Electronic address: walther.mothes@yale.edu.
Cell Host Microbe ; 28(6): 880-891.e8, 2020 12 09.
Article in English | MEDLINE | ID: covidwho-921850
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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ABSTRACT
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 (Förster) 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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Protein Conformation / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 Topics: Vaccines Limits: Humans Language: English Journal: Cell Host Microbe Journal subject: Microbiology Year: 2020 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Protein Conformation / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 Topics: Vaccines Limits: Humans Language: English Journal: Cell Host Microbe Journal subject: Microbiology Year: 2020 Document Type: Article