دورية أكاديمية
Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion.
| العنوان: | Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion. |
|---|---|
| المؤلفون: | Benton DJ; Strutural Biology of Disease Processes Laboratory, Francis Crick Institute, London, UK. donald.benton@crick.ac.uk., Wrobel AG; Strutural Biology of Disease Processes Laboratory, Francis Crick Institute, London, UK. antoni.wrobel@crick.ac.uk., Xu P; Precision Medicine Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.; Francis Crick Institute, London, UK., Roustan C; Structural Biology Science Technology Platform, Francis Crick Institute, London, UK., Martin SR; Strutural Biology of Disease Processes Laboratory, Francis Crick Institute, London, UK., Rosenthal PB; Structural Biology of Cells and Viruses Laboratory, Francis Crick Institute, London, UK., Skehel JJ; Strutural Biology of Disease Processes Laboratory, Francis Crick Institute, London, UK., Gamblin SJ; Strutural Biology of Disease Processes Laboratory, Francis Crick Institute, London, UK. steve.gamblin@crick.ac.uk. |
| المصدر: | Nature [Nature] 2020 Dec; Vol. 588 (7837), pp. 327-330. Date of Electronic Publication: 2020 Sep 17. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Basingstoke : Nature Publishing Group Original Publication: London, Macmillan Journals ltd. |
| مواضيع طبية MeSH: | Protein Binding*, Angiotensin-Converting Enzyme 2/*chemistry , Angiotensin-Converting Enzyme 2/*metabolism , Membrane Fusion/*physiology , Receptors, Coronavirus/*metabolism , Spike Glycoprotein, Coronavirus/*chemistry , Spike Glycoprotein, Coronavirus/*metabolism, Angiotensin-Converting Enzyme 2/ultrastructure ; Cryoelectron Microscopy ; Furin/metabolism ; Humans ; Models, Molecular ; Protein Folding ; Protein Subunits/chemistry ; Protein Subunits/metabolism ; Proteolysis ; Receptors, Coronavirus/chemistry ; Receptors, Coronavirus/ultrastructure ; Spike Glycoprotein, Coronavirus/ultrastructure |
| مستخلص: | Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is initiated by virus binding to the ACE2 cell-surface receptors 1-4 , followed by fusion of the virus and cell membranes to release the virus genome into the cell. Both receptor binding and membrane fusion activities are mediated by the virus spike glycoprotein 5-7 . As with other class-I membrane-fusion proteins, the spike protein is post-translationally cleaved, in this case by furin, into the S1 and S2 components that remain associated after cleavage 8-10 . Fusion activation after receptor binding is proposed to involve the exposure of a second proteolytic site (S2'), cleavage of which is required for the release of the fusion peptide 11,12 . Here we analyse the binding of ACE2 to the furin-cleaved form of the SARS-CoV-2 spike protein using cryo-electron microscopy. We classify ten different molecular species, including the unbound, closed spike trimer, the fully open ACE2-bound trimer and dissociated monomeric S1 bound to ACE2. The ten structures describe ACE2-binding events that destabilize the spike trimer, progressively opening up, and out, the individual S1 components. The opening process reduces S1 contacts and unshields the trimeric S2 core, priming the protein for fusion activation and dissociation of ACE2-bound S1 monomers. The structures also reveal refolding of an S1 subdomain after ACE2 binding that disrupts interactions with S2, which involves Asp614 13-15 and leads to the destabilization of the structure of S2 proximal to the secondary (S2') cleavage site. |
| References: | Proc Natl Acad Sci U S A. 2017 Aug 29;114(35):E7348-E7357. (PMID: 28807998) Cell Res. 2017 Jan;27(1):119-129. (PMID: 28008928) J Comput Chem. 2004 Oct;25(13):1605-12. (PMID: 15264254) Cell. 2020 Aug 20;182(4):812-827.e19. (PMID: 32697968) Nat Struct Mol Biol. 2019 Jun;26(6):481-489. (PMID: 31160783) IUCrJ. 2019 Jan 01;6(Pt 1):5-17. (PMID: 30713699) Nature. 2020 May;581(7807):221-224. (PMID: 32225175) J Mol Biol. 2007 Sep 21;372(3):774-97. (PMID: 17681537) Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501. (PMID: 20383002) J Mol Biol. 2017 Dec 8;429(24):3875-3892. (PMID: 29056462) Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21. (PMID: 20124702) IUCrJ. 2019 Jun 27;6(Pt 4):526-531. (PMID: 31316797) Nat Commun. 2017 Apr 10;8:15092. (PMID: 28393837) J Struct Biol. 2012 Dec;180(3):519-30. (PMID: 23000701) Nature. 2020 Mar;579(7798):270-273. (PMID: 32015507) Science. 2020 Mar 13;367(6483):1260-1263. (PMID: 32075877) J Struct Biol. 2015 Nov;192(2):216-21. (PMID: 26278980) Nat Methods. 2017 Mar;14(3):290-296. (PMID: 28165473) Cell. 2020 Apr 16;181(2):281-292.e6. (PMID: 32155444) Annu Rev Virol. 2016 Sep 29;3(1):237-261. (PMID: 27578435) Nature. 2003 Nov 27;426(6965):450-4. (PMID: 14647384) Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5871-6. (PMID: 19321428) J Mol Biol. 2003 Oct 31;333(4):721-45. (PMID: 14568533) Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):386-94. (PMID: 21460457) J Virol. 2020 Mar 17;94(7):. (PMID: 31996437) Science. 2020 Sep 25;369(6511):1586-1592. (PMID: 32694201) Proc Natl Acad Sci U S A. 2017 Oct 17;114(42):11157-11162. (PMID: 29073020) Nature. 2020 Jul;583(7814):150-153. (PMID: 32461688) Nature. 2016 Mar 3;531(7592):114-117. (PMID: 26855426) Nat Struct Mol Biol. 2020 Aug;27(8):763-767. (PMID: 32647346) Science. 2005 Sep 16;309(5742):1864-8. (PMID: 16166518) Science. 2020 Mar 27;367(6485):1444-1448. (PMID: 32132184) PLoS Pathog. 2018 Aug 13;14(8):e1007236. (PMID: 30102747) Commun Biol. 2019 Jun 19;2:218. (PMID: 31240256) Nat Methods. 2017 Apr;14(4):331-332. (PMID: 28250466) Cell. 2020 Aug 20;182(4):828-842.e16. (PMID: 32645326) Nat Commun. 2020 Jul 17;11(1):3618. (PMID: 32681106) J Struct Biol. 2013 Nov;184(2):226-36. (PMID: 23954653) Proc Natl Acad Sci U S A. 2014 Oct 21;111(42):15214-9. (PMID: 25288733) Cell. 2020 Apr 16;181(2):271-280.e8. (PMID: 32142651) Nature. 2020 May;581(7807):215-220. (PMID: 32225176) Sci Rep. 2018 Oct 24;8(1):15701. (PMID: 30356097) |
| معلومات مُعتمدة: | FC001078 United Kingdom ARC_ Arthritis Research UK; FC001143 United Kingdom MRC_ Medical Research Council; FC001143 United Kingdom WT_ Wellcome Trust; FC001143 United Kingdom ARC_ Arthritis Research UK; FC001078 United Kingdom CRUK_ Cancer Research UK; FC001143 United Kingdom CRUK_ Cancer Research UK; FC001078 United Kingdom WT_ Wellcome Trust; FC001078 United Kingdom MRC_ Medical Research Council; United Kingdom WT_ Wellcome Trust |
| المشرفين على المادة: | 0 (Protein Subunits) 0 (Receptors, Coronavirus) 0 (Spike Glycoprotein, Coronavirus) 0 (spike protein, SARS-CoV-2) EC 3.4.17.23 (ACE2 protein, human) EC 3.4.17.23 (Angiotensin-Converting Enzyme 2) EC 3.4.21.75 (Furin) |
| تواريخ الأحداث: | Date Created: 20200917 Date Completed: 20201211 Latest Revision: 20240216 |
| رمز التحديث: | 20240216 |
| مُعرف محوري في PubMed: | PMC7116727 |
| DOI: | 10.1038/s41586-020-2772-0 |
| PMID: | 32942285 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1476-4687 |
|---|---|
| DOI: | 10.1038/s41586-020-2772-0 |