دورية أكاديمية
Evolution of the SARS-CoV-2 spike protein in the human host.
| العنوان: | Evolution of the SARS-CoV-2 spike protein in the human host. |
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| المؤلفون: | Wrobel AG; Structural Biology of Disease Processes Laboratory, NW1 1AT, London, UK. antoni.wrobel@crick.ac.uk., Benton DJ; Structural Biology of Disease Processes Laboratory, NW1 1AT, London, UK. donald.benton@crick.ac.uk., Roustan C; Structural Biology Science Technology Platform, NW1 1AT, London, UK., Borg A; Structural Biology Science Technology Platform, NW1 1AT, London, UK., Hussain S; Worldwide Influenza Centre, NW1 1AT, London, UK.; RNA Virus Replication Laboratory, NW1 1AT, London, UK., Martin SR; Structural Biology of Disease Processes Laboratory, NW1 1AT, London, UK., Rosenthal PB; Structural Biology of Cells and Viruses Laboratory; Francis Crick Institute, NW1 1AT, London, UK., Skehel JJ; Structural Biology of Disease Processes Laboratory, NW1 1AT, London, UK., Gamblin SJ; Structural Biology of Disease Processes Laboratory, NW1 1AT, London, UK. steve.gamblin@crick.ac.uk. |
| المصدر: | Nature communications [Nat Commun] 2022 Mar 04; Vol. 13 (1), pp. 1178. Date of Electronic Publication: 2022 Mar 04. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [London] : Nature Pub. Group |
| مواضيع طبية MeSH: | Mutation, Missense*, Angiotensin-Converting Enzyme 2/*metabolism , COVID-19/*metabolism , SARS-CoV-2/*genetics , Spike Glycoprotein, Coronavirus/*genetics, Angiotensin-Converting Enzyme 2/chemistry ; Angiotensin-Converting Enzyme 2/ultrastructure ; Binding Sites/genetics ; COVID-19/transmission ; COVID-19/virology ; Cryoelectron Microscopy ; Cytopathogenic Effect, Viral/genetics ; Evolution, Molecular ; Host-Pathogen Interactions ; Humans ; Kinetics ; Models, Molecular ; Protein Binding ; Protein Domains ; SARS-CoV-2/metabolism ; SARS-CoV-2/physiology ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/metabolism |
| مستخلص: | Recently emerged variants of SARS-CoV-2 contain in their surface spike glycoproteins multiple substitutions associated with increased transmission and resistance to neutralising antibodies. We have examined the structure and receptor binding properties of spike proteins from the B.1.1.7 (Alpha) and B.1.351 (Beta) variants to better understand the evolution of the virus in humans. Spikes of both variants have the same mutation, N501Y, in the receptor-binding domains. This substitution confers tighter ACE2 binding, dependent on the common earlier substitution, D614G. Each variant spike has acquired other key changes in structure that likely impact virus pathogenesis. The spike from the Alpha variant is more stable against disruption upon binding ACE2 receptor than all other spikes studied. This feature is linked to the acquisition of a more basic substitution at the S1-S2 furin site (also observed for the variants of concern Delta, Kappa, and Omicron) which allows for near-complete cleavage. In the Beta variant spike, the presence of a new substitution, K417N (also observed in the Omicron variant), in combination with the D614G, stabilises a more open spike trimer, a conformation required for receptor binding. Our observations suggest ways these viruses have evolved to achieve greater transmissibility in humans. (© 2022. The Author(s).) |
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| معلومات مُعتمدة: | FC001143 United Kingdom WT_ Wellcome Trust; FC001078 United Kingdom ARC_ Arthritis Research UK; FC001030 United Kingdom ARC_ Arthritis Research UK; FC001143 United Kingdom ARC_ Arthritis Research UK; United Kingdom WT_ Wellcome Trust; FC001078 United Kingdom WT_ Wellcome Trust; FC001030 United Kingdom WT_ Wellcome Trust |
| المشرفين على المادة: | 0 (Spike Glycoprotein, Coronavirus) 0 (spike protein, SARS-CoV-2) EC 3.4.17.23 (Angiotensin-Converting Enzyme 2) |
| SCR Organism: | SARS-CoV-2 variants |
| تواريخ الأحداث: | Date Created: 20220305 Date Completed: 20220321 Latest Revision: 20220321 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC8897445 |
| DOI: | 10.1038/s41467-022-28768-w |
| PMID: | 35246509 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 2041-1723 |
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| DOI: | 10.1038/s41467-022-28768-w |