6zp5
From Proteopedia
(Difference between revisions)
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<StructureSection load='6zp5' size='340' side='right'caption='[[6zp5]], [[Resolution|resolution]] 3.10Å' scene=''> | <StructureSection load='6zp5' size='340' side='right'caption='[[6zp5]], [[Resolution|resolution]] 3.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'> | + | <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 [https://proteopedia.org/fgij/fg.htm?mol=6ZP5 FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.1Å</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> | <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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| - | + | With the help of novel processing workflows and algorithms, we have obtained a better understanding of the flexibility and conformational dynamics of the SARS-CoV-2 spike in the prefusion state. We have re-analyzed previous cryo-EM data combining 3D clustering approaches with ways to explore a continuous flexibility space based on 3D Principal Component Analysis. These advanced analyses revealed a concerted motion involving the receptor-binding domain (RBD), N-terminal domain (NTD), and subdomain 1 and 2 (SD1 & SD2) around the previously characterized 1-RBD-up state, which have been modeled as elastic deformations. We show that in this dataset there are not well-defined, stable, spike conformations, but virtually a continuum of states moving in a concerted fashion. We obtained an improved resolution ensemble map with minimum bias, from which we model by flexible fitting the extremes of the change along the direction of maximal variance. Moreover, a high-resolution structure of a recently described biochemically stabilized form of the spike is shown to greatly reduce the dynamics observed for the wild-type spike. Our results provide new detailed avenues to potentially restrain the spike dynamics for structure-based drug and vaccine design and at the same time give a warning of the potential image processing classification instability of these complicated datasets, having a direct impact on the interpretability of the results. | |
| - | Continuous flexibility analysis of SARS-CoV-2 | + | 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 bioRxiv. 2020 Jul 8. doi: 10.1101/2020.07.08.191072. PMID:32676604<ref>PMID:32676604</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
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</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]] | ||
Current revision
SARS-CoV-2 spike in prefusion state (flexibility analysis, 1-up closed conformation)
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