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| | ==X-ray crystal structure of the SARS coronavirus spike receptor binding domain in complex with F26G19 Fab== | | ==X-ray crystal structure of the SARS coronavirus spike receptor binding domain in complex with F26G19 Fab== |
| - | <StructureSection load='3bgf' size='340' side='right' caption='[[3bgf]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='3bgf' size='340' side='right'caption='[[3bgf]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3bgf]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Cvhsa Cvhsa] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BGF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BGF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3bgf]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome-related_coronavirus Severe acute respiratory syndrome-related coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BGF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BGF FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ajf|2ajf]], [[2dd8|2dd8]], [[2ghw|2ghw]], [[2ghv|2ghv]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3Å</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>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bgf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bgf OCA], [https://pdbe.org/3bgf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bgf RCSB], [https://www.ebi.ac.uk/pdbsum/3bgf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bgf ProSAT]</span></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=3bgf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bgf OCA], [http://pdbe.org/3bgf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3bgf RCSB], [http://www.ebi.ac.uk/pdbsum/3bgf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3bgf 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_SARS SPIKE_SARS] May down-regulate host tetherin (BST2) by lysosomal degradation, thereby counteracting its antiviral activity.<ref>PMID:31199522</ref> Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 and CLEC4M/DC-SIGNR receptors and internalization of the virus into the endosomes of the host cell induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membrane fusion within endosomes.[HAMAP-Rule:MF_04099]<ref>PMID:14670965</ref> <ref>PMID:15496474</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]<ref>PMID:19321428</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bg/3bgf_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bg/3bgf_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | ==See Also== | | ==See Also== |
| - | *[[3D structures of monoclonal antibody|3D structures of monoclonal antibody]] | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | + | *[[Sandbox 3001|Sandbox 3001]] |
| | + | *[[Spike protein 3D structures|Spike protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cvhsa]] | + | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: Pak, J E]] | + | [[Category: Severe acute respiratory syndrome-related coronavirus]] |
| - | [[Category: Rini, J M]]
| + | [[Category: Pak JE]] |
| - | [[Category: Antigen-antibody complex]]
| + | [[Category: Rini JM]] |
| - | [[Category: Envelope protein]] | + | |
| - | [[Category: Glycoprotein]] | + | |
| - | [[Category: Host-virus interaction]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| - | [[Category: Viral protein-immune system complex]]
| + | |
| - | [[Category: Virion]]
| + | |
| - | [[Category: Virulence]]
| + | |
| Structural highlights
Function
SPIKE_SARS May down-regulate host tetherin (BST2) by lysosomal degradation, thereby counteracting its antiviral activity.[1] Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 and CLEC4M/DC-SIGNR receptors and internalization of the virus into the endosomes of the host cell induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membrane fusion within endosomes.[HAMAP-Rule:MF_04099][2] [3] 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][4]
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 spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) is responsible for host cell attachment and fusion of the viral and host cell membranes. Within S the receptor binding domain (RBD) mediates the interaction with angiotensin-converting enzyme 2 (ACE2), the SARS-CoV host cell receptor. Both S and the RBD are highly immunogenic and both have been found to elicit neutralizing antibodies. Reported here is the X-ray crystal structure of the RBD in complex with the Fab of a neutralizing mouse monoclonal antibody, F26G19, elicited by immunization with chemically inactivated SARS-CoV. The RBD-F26G19 Fab complex represents the first example of the structural characterization of an antibody elicited by an immune response to SARS-CoV or any fragment of it. The structure reveals that the RBD surface recognized by F26G19 overlaps significantly with the surface recognized by ACE2 and, as such, suggests that F26G19 likely neutralizes SARS-CoV by blocking the virus-host cell interaction.
Structural insights into immune recognition of the severe acute respiratory syndrome coronavirus S protein receptor binding domain.,Pak JE, Sharon C, Satkunarajah M, Auperin TC, Cameron CM, Kelvin DJ, Seetharaman J, Cochrane A, Plummer FA, Berry JD, Rini JM J Mol Biol. 2009 May 15;388(4):815-23. Epub 2009 Mar 24. PMID:19324051[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wang SM, Huang KJ, Wang CT. Severe acute respiratory syndrome coronavirus spike protein counteracts BST2-mediated restriction of virus-like particle release. J Med Virol. 2019 Oct;91(10):1743-1750. doi: 10.1002/jmv.25518. Epub 2019 Jul 10. PMID:31199522 doi:http://dx.doi.org/10.1002/jmv.25518
- ↑ Wong SK, Li W, Moore MJ, Choe H, Farzan M. A 193-amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2. J Biol Chem. 2004 Jan 30;279(5):3197-201. Epub 2003 Dec 11. PMID:14670965 doi:http://dx.doi.org/10.1074/jbc.C300520200
- ↑ Jeffers SA, Tusell SM, Gillim-Ross L, Hemmila EM, Achenbach JE, Babcock GJ, Thomas WD Jr, Thackray LB, Young MD, Mason RJ, Ambrosino DM, Wentworth DE, Demartini JC, Holmes KV. CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15748-53. doi:, 10.1073/pnas.0403812101. Epub 2004 Oct 20. PMID:15496474 doi:http://dx.doi.org/10.1073/pnas.0403812101
- ↑ Belouzard S, Chu VC, Whittaker GR. Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites. Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5871-6. doi:, 10.1073/pnas.0809524106. Epub 2009 Mar 24. PMID:19321428 doi:http://dx.doi.org/10.1073/pnas.0809524106
- ↑ Pak JE, Sharon C, Satkunarajah M, Auperin TC, Cameron CM, Kelvin DJ, Seetharaman J, Cochrane A, Plummer FA, Berry JD, Rini JM. Structural insights into immune recognition of the severe acute respiratory syndrome coronavirus S protein receptor binding domain. J Mol Biol. 2009 May 15;388(4):815-23. Epub 2009 Mar 24. PMID:19324051 doi:10.1016/j.jmb.2009.03.042
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