Real-Time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles
| العنوان: | Real-Time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles |
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| المؤلفون: | Scott C. Blanchard, Andrés Finzi, Wei Shi, Peter D. Kwong, Guillaume Beaudoin-Bussières, John R. Mascola, Walther Mothes, Annemarie Laumaea, Romain Gasser, Daniel S. Terry, Wenwei Li, Desheng Zheng, Lihong Liu, Sai Priya Anand, David D. Ho, Jérémie Prévost, Tongqing Zhou, Jason Gorman, Maolin Lu, Jonathan R. Grover, Shilei Ding, Pradeep D. Uchil, Baoshan Zhang |
| المصدر: | Cell Host & Microbe bioRxiv |
| بيانات النشر: | Elsevier BV, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | real-time conformational dynamics, Immunogen, Protein Conformation, Trimer, Antibodies, Viral, 01 natural sciences, Neutralization, Epitopes, 0302 clinical medicine, Protein structure, antibody neutralization, Furin, chemistry.chemical_classification, 0303 health sciences, Membrane Glycoproteins, biology, receptor ACE2, Chemistry, Antibodies, Monoclonal, Single-molecule FRET, Trypsin, SARS-CoV-2 spike protein, 3. Good health, Spike Glycoprotein, Coronavirus, Receptors, Virus, Protein Binding, medicine.drug, Proteases, Allosteric regulation, 010402 general chemistry, single-molecule FRET, Microbiology, Virus, Article, 03 medical and health sciences, Viral entry, Virology, medicine, Humans, 030304 developmental biology, SARS-CoV-2, Virion, COVID-19, Virus Internalization, 0104 chemical sciences, Enzyme, Förster resonance energy transfer, Biophysics, biology.protein, Parasitology, 030217 neurology & neurosurgery |
| الوصف: | 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. Graphical Abstract Highlights • SARS-CoV-2 S protein dynamically samples at least 4 distinct conformational states • hACE2 activates S from the ground state to the activated state via an intermediate • Proteolytic processing of S accelerates hACE2-dependent activation • Antibodies can antagonize S by two different mechanisms of neutralization The SARS-CoV-2 spike protein has been observed to adopt different structural states. Lu et al. directly visualize the conformational dynamics of spike protein on the surface of virus particles and describe how the conformational landscape changes upon activation by the host receptor or antagonism by antibodies. |
| اللغة: | English |
| تدمد: | 1931-3128 |
| DOI: | 10.1016/j.chom.2020.11.001 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e0d7fb2d0ccb51f8e91a4fa440c1f2c2 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e0d7fb2d0ccb51f8e91a4fa440c1f2c2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19313128 |
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| DOI: | 10.1016/j.chom.2020.11.001 |