6zp5
From Proteopedia
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==SARS-CoV-2 spike in prefusion state (flexibility analysis, 1-up closed conformation)== | ==SARS-CoV-2 spike in prefusion state (flexibility analysis, 1-up closed conformation)== | ||
| - | <StructureSection load='6zp5' size='340' side='right'caption='[[6zp5]]' scene=''> | + | <StructureSection load='6zp5' size='340' side='right'caption='[[6zp5]], [[Resolution|resolution]] 3.10Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZP5 OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6zp5]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZP5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZP5 FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6zp5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zp5 OCA], [https://pdbe.org/6zp5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zp5 RCSB], [https://www.ebi.ac.uk/pdbsum/6zp5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zp5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/SPIKE_SARS2 SPIKE_SARS2] attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 receptor and internalization of the virus into the endosomes of the host cell induces conformational changes in the Spike glycoprotein (PubMed:32142651, PubMed:32075877, PubMed:32155444). Uses also human TMPRSS2 for priming in human lung cells which is an essential step for viral entry (PubMed:32142651). Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes.[HAMAP-Rule:MF_04099]<ref>PMID:32075877</ref> <ref>PMID:32142651</ref> <ref>PMID:32155444</ref> mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.[HAMAP-Rule:MF_04099] Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Using a new consensus-based image-processing approach together with principal component analysis, the flexibility and conformational dynamics of the SARS-CoV-2 spike in the prefusion state have been analysed. These studies revealed concerted motions involving the receptor-binding domain (RBD), N-terminal domain, and subdomains 1 and 2 around the previously characterized 1-RBD-up state, which have been modeled as elastic deformations. It is shown that in this data set there are not well defined, stable spike conformations, but virtually a continuum of states. An ensemble map was obtained with minimum bias, from which the extremes of the change along the direction of maximal variance were modeled by flexible fitting. The results provide a warning of the potential image-processing classification instability of these complicated data sets, which has a direct impact on the interpretability of the results. | ||
| + | |||
| + | Continuous flexibility analysis of SARS-CoV-2 spike prefusion structures.,Melero R, Sorzano COS, Foster B, Vilas JL, Martinez M, Marabini R, Ramirez-Aportela E, Sanchez-Garcia R, Herreros D, Del Cano L, Losana P, Fonseca-Reyna YC, Conesa P, Wrapp D, Chacon P, McLellan JS, Tagare HD, Carazo JM IUCrJ. 2020 Sep 29;7(Pt 6):1059-69. doi: 10.1107/S2052252520012725. PMID:33063791<ref>PMID:33063791</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6zp5" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| + | [[Category: Severe acute respiratory syndrome coronavirus 2]] | ||
[[Category: Carazo JM]] | [[Category: Carazo JM]] | ||
[[Category: Marabini R]] | [[Category: Marabini R]] | ||
[[Category: Martinez M]] | [[Category: Martinez M]] | ||
Revision as of 10:05, 21 December 2022
SARS-CoV-2 spike in prefusion state (flexibility analysis, 1-up closed conformation)
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