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| | ==Solution Structure of the SARS-Coronavirus HR2 Domain== | | ==Solution Structure of the SARS-Coronavirus HR2 Domain== |
| - | <StructureSection load='2fxp' size='340' side='right' caption='[[2fxp]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | + | <StructureSection load='2fxp' size='340' side='right'caption='[[2fxp]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2fxp]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Cvhsa Cvhsa]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FXP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FXP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2fxp]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Cvhsa Cvhsa]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FXP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FXP FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">S ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227859 CVHSA])</td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">S ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227859 CVHSA])</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=2fxp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fxp OCA], [http://pdbe.org/2fxp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2fxp RCSB], [http://www.ebi.ac.uk/pdbsum/2fxp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2fxp 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=2fxp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fxp OCA], [https://pdbe.org/2fxp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fxp RCSB], [https://www.ebi.ac.uk/pdbsum/2fxp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fxp ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SPIKE_CVHSA 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. | + | [[https://www.uniprot.org/uniprot/SPIKE_CVHSA 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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 2fxp" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 2fxp" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Sandbox 3001|Sandbox 3001]] |
| | + | *[[Spike protein|Spike protein]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Cvhsa]] | | [[Category: Cvhsa]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Caffrey, M]] | | [[Category: Caffrey, M]] |
| | [[Category: Hakansson-McReynolds, S]] | | [[Category: Hakansson-McReynolds, S]] |
| Structural highlights
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
The envelope glycoprotein, termed the spike protein, of severe acute respiratory syndrome coronavirus (SARS-CoV) is known to mediate viral entry. Similar to other class 1 viral fusion proteins, the heptad repeat regions of SARS-CoV spike are thought to undergo conformational changes from a prefusion form to a subsequent post-fusion form that enables fusion of the viral and host membranes. Recently, the structure of a post-fusion form of SARS-CoV spike, which consists of isolated domains of heptad repeats 1 and 2 (HR1 and HR2), has been determined by x-ray crystallography. To date there is no structural information for the prefusion conformations of SARS-CoV HR1 and HR2. In this work we present the NMR structure of the HR2 domain (residues 1141-1193) from SARS-CoV (termed S2-HR2) in the presence of the co-solvent trifluoroethanol. We find that in the absence of HR1, S2-HR2 forms a coiled coil symmetric trimer with a complex molecular mass of 18 kDa. The S2-HR2 structure, which is the first example of the prefusion form of coronavirus envelope, supports the current model of viral membrane fusion and gives insight into the design of structure-based antagonists of SARS.
Solution structure of the severe acute respiratory syndrome-coronavirus heptad repeat 2 domain in the prefusion state.,Hakansson-McReynolds S, Jiang S, Rong L, Caffrey M J Biol Chem. 2006 Apr 28;281(17):11965-71. Epub 2006 Feb 28. PMID:16507566[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hakansson-McReynolds S, Jiang S, Rong L, Caffrey M. Solution structure of the severe acute respiratory syndrome-coronavirus heptad repeat 2 domain in the prefusion state. J Biol Chem. 2006 Apr 28;281(17):11965-71. Epub 2006 Feb 28. PMID:16507566 doi:10.1074/jbc.M601174200
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