7my8
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
==Fusion Peptide of SARS-CoV-2 Spike Rearranges into a Wedge Inserted in Bilayered Micelles== | ==Fusion Peptide of SARS-CoV-2 Spike Rearranges into a Wedge Inserted in Bilayered Micelles== | ||
| - | <StructureSection load='7my8' size='340' side='right'caption='[[7my8]]' scene=''> | + | <StructureSection load='7my8' size='340' side='right'caption='[[7my8]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full | + | <table><tr><td colspan='2'>[[7my8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/2019-ncov 2019-ncov]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MY8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MY8 FirstGlance]. <br> |
| - | </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=7my8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7my8 OCA], [https://pdbe.org/7my8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7my8 RCSB], [https://www.ebi.ac.uk/pdbsum/7my8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7my8 ProSAT]</span></td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">S, 2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2697049 2019-nCoV])</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=7my8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7my8 OCA], [https://pdbe.org/7my8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7my8 RCSB], [https://www.ebi.ac.uk/pdbsum/7my8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7my8 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 == | ||
| + | The receptor binding and proteolysis of Spike of SARS-CoV-2 release its S2 subunit to rearrange and catalyze viral-cell fusion. This deploys the fusion peptide for insertion into the cell membranes targeted. We show that this fusion peptide transforms from intrinsic disorder in solution into a wedge-shaped structure inserted in bilayered micelles, according to chemical shifts, (15)N NMR relaxation, and NOEs. The globular fold of three helices contrasts the open, extended forms of this region observed in the electron density of compact prefusion states. In the hydrophobic, narrow end of the wedge, helices 1 and 2 contact the fatty acyl chains of phospholipids, according to NOEs and proximity to a nitroxide spin label deep in the membrane mimic. The polar end of the wedge may engage and displace lipid head groups and bind Ca(2+) ions for membrane fusion. Polar helix 3 protrudes from the bilayer where it might be accessible to antibodies. | ||
| + | |||
| + | Fusion Peptide of SARS-CoV-2 Spike Rearranges into a Wedge Inserted in Bilayered Micelles.,Koppisetti RK, Fulcher YG, Van Doren SR J Am Chem Soc. 2021 Aug 10. doi: 10.1021/jacs.1c05435. PMID:34375093<ref>PMID:34375093</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7my8" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: 2019-ncov]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Fulcher | + | [[Category: Doren, S R.Van]] |
| - | [[Category: Koppisetti | + | [[Category: Fulcher, Y G]] |
| - | [[Category: | + | [[Category: Koppisetti, R K]] |
| + | [[Category: Fusion peptide]] | ||
| + | [[Category: Lipid binding protein]] | ||
Revision as of 06:36, 25 August 2021
Fusion Peptide of SARS-CoV-2 Spike Rearranges into a Wedge Inserted in Bilayered Micelles
| |||||||||||
