1wnc

From Proteopedia

(Difference between revisions)

Revision as of 14:25, 12 October 2017

Crystal structure of the SARS-CoV Spike protein fusion core

Structural highlights

1wnc is a 6 chain structure with sequence from Cvhsa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[SPIKE_CVHSA] S1 attaches the virion to the cell membrane by interacting with human ACE2 and CLEC4M/DC-SIGNR, initiating the infection. Binding to the receptor and internalization of the virus into the endosomes of the host cell probably induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes. S2 is 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.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Severe acute respiratory syndrome coronavirus is a newly emergent virus responsible for a recent outbreak of an atypical pneumonia. The coronavirus spike protein, an enveloped glycoprotein essential for viral entry, belongs to the class I fusion proteins and is characterized by the presence of two heptad repeat (HR) regions, HR1 and HR2. These two regions are understood to form a fusion-active conformation similar to those of other typical viral fusion proteins. This hairpin structure likely juxtaposes the viral and cellular membranes, thus facilitating membrane fusion and subsequent viral entry. The fusion core protein of severe acute respiratory syndrome coronavirus spike protein was crystallized, and the structure was determined at 2.8 A of resolution. The fusion core is a six-helix bundle with three HR2 helices packed against the hydrophobic grooves on the surface of central coiled coil formed by three parallel HR1 helices in an oblique antiparallel manner. This structure shares significant similarity with the fusion core structure of mouse hepatitis virus spike protein and other viral fusion proteins, suggesting a conserved mechanism of membrane fusion. Drug discovery strategies aimed at inhibiting viral entry by blocking hairpin formation, which have been successfully used in human immunodeficiency virus 1 inhibitor development, may be applicable to the inhibition of severe acute respiratory syndrome coronavirus on the basis of structural information provided here. The relatively deep grooves on the surface of the central coiled coil will be a good target site for the design of viral fusion inhibitors.

Crystal structure of severe acute respiratory syndrome coronavirus spike protein fusion core.,Xu Y, Lou Z, Liu Y, Pang H, Tien P, Gao GF, Rao Z J Biol Chem. 2004 Nov 19;279(47):49414-9. Epub 2004 Sep 1. PMID:15345712^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Xu Y, Lou Z, Liu Y, Pang H, Tien P, Gao GF, Rao Z. Crystal structure of severe acute respiratory syndrome coronavirus spike protein fusion core. J Biol Chem. 2004 Nov 19;279(47):49414-9. Epub 2004 Sep 1. PMID:15345712 doi:10.1074/jbc.M408782200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1wnc"

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 ==Crystal structure of the SARS-CoV Spike protein fusion core==
 <StructureSection load='1wnc' size='340' side='right' caption='[[1wnc]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1wnc]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Cvhsa Cvhsa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WNC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WNC FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wnc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wnc OCA], [http://pdbe.org/1wnc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1wnc RCSB], [http://www.ebi.ac.uk/pdbsum/1wnc PDBsum]</span></td></tr>
+</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wnc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wnc OCA], [http://pdbe.org/1wnc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1wnc RCSB], [http://www.ebi.ac.uk/pdbsum/1wnc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1wnc ProSAT]</span></td></tr>
 </table>
 == Function ==

1wnc

From Proteopedia

Revision as of 14:25, 12 October 2017

Crystal structure of the SARS-CoV Spike protein fusion core

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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