6b3o: Difference between revisions
New page: ==Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion== <StructureSection load='6b3o' size='340' side='right' caption='6b3o, [[Resolution|resol... |
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==Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion== | ==Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion== | ||
< | <SX load='6b3o' size='340' side='right' viewer='molstar' caption='[[6b3o]], [[Resolution|resolution]] 4.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6b3o]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B3O OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[6b3o]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Cvma5 Cvma5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B3O OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6B3O FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">S, 3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11142 CVMA5])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6b3o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b3o OCA], [http://pdbe.org/6b3o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b3o RCSB], [http://www.ebi.ac.uk/pdbsum/6b3o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b3o ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/SPIKE_CVMA5 SPIKE_CVMA5]] S1 attaches the virion to the cell membrane by interacting with murine CEACAM1, initiating the infection.<ref>PMID:16014947</ref> S2 is a class I viral fusion protein. Under the current model, the protein has at least 3 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 plasma cell membranes. Presumably interacts with target cell lipid raft after cell attachment.<ref>PMID:16014947</ref> | [[http://www.uniprot.org/uniprot/SPIKE_CVMA5 SPIKE_CVMA5]] S1 attaches the virion to the cell membrane by interacting with murine CEACAM1, initiating the infection.<ref>PMID:16014947</ref> S2 is a class I viral fusion protein. Under the current model, the protein has at least 3 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 plasma cell membranes. Presumably interacts with target cell lipid raft after cell attachment.<ref>PMID:16014947</ref> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The tremendous pandemic potential of coronaviruses was demonstrated twice in the past few decades by two global outbreaks of deadly pneumonia. The coronavirus spike (S) glycoprotein initiates infection by promoting fusion of the viral and cellular membranes through conformational changes that remain largely uncharacterized. Here we report the cryoEM structure of a coronavirus S glycoprotein in the postfusion state, showing large-scale secondary, tertiary, and quaternary rearrangements compared with the prefusion trimer and rationalizing the free-energy landscape of this conformational machine. We also biochemically characterized the molecular events associated with refolding of the metastable prefusion S glycoprotein to the postfusion conformation using limited proteolysis, mass spectrometry, and single-particle EM. The observed similarity between postfusion coronavirus S and paramyxovirus F structures demonstrates that a conserved refolding trajectory mediates entry of these viruses and supports the evolutionary relatedness of their fusion subunits. Finally, our data provide a structural framework for understanding the mode of neutralization of antibodies targeting the fusion machinery and for engineering next-generation subunit vaccines or inhibitors against this medically important virus family. | |||
Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion.,Walls AC, Tortorici MA, Snijder J, Xiong X, Bosch BJ, Rey FA, Veesler D Proc Natl Acad Sci U S A. 2017 Oct 17;114(42):11157-11162. doi:, 10.1073/pnas.1708727114. Epub 2017 Oct 3. PMID:29073020<ref>PMID:29073020</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6b3o" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Spike protein|Spike protein]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</ | </SX> | ||
[[Category: Cvma5]] | |||
[[Category: Large Structures]] | |||
[[Category: Bosch, B J]] | [[Category: Bosch, B J]] | ||
[[Category: Rey, F A]] | [[Category: Rey, F A]] | ||