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| | ==Crystal structure of potent neutralizing antibody m336 in complex with MERS Co-V RBD== | | ==Crystal structure of potent neutralizing antibody m336 in complex with MERS Co-V RBD== |
| - | <StructureSection load='4xak' size='340' side='right' caption='[[4xak]], [[Resolution|resolution]] 2.45Å' scene=''> | + | <StructureSection load='4xak' size='340' side='right'caption='[[4xak]], [[Resolution|resolution]] 2.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4xak]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Betacoronavirus_england_1 Betacoronavirus england 1] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XAK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XAK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4xak]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Betacoronavirus_England_1 Betacoronavirus England 1] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XAK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XAK FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=1263720 Betacoronavirus England 1])</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=4xak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xak OCA], [https://pdbe.org/4xak PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xak RCSB], [https://www.ebi.ac.uk/pdbsum/4xak PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xak 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=4xak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xak OCA], [http://pdbe.org/4xak PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xak RCSB], [http://www.ebi.ac.uk/pdbsum/4xak PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xak ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SPIKE_CVEMC SPIKE_CVEMC]] S1 attaches the virion to the cell membrane by interacting with host DPP4, initiating the infection.<ref>PMID:23486063</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 (By similarity). | + | [https://www.uniprot.org/uniprot/SPIKE_MERS1 SPIKE_MERS1] Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Interacts with host DPP4 to mediate virla entry.[HAMAP-Rule:MF_04099]<ref>PMID:23486063</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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[3D structures of antibody|3D structures of antibody]] | + | *[[Antibody 3D structures|Antibody 3D structures]] |
| | + | *[[Sandbox 3001|Sandbox 3001]] |
| | + | *[[Spike protein|Spike protein]] |
| | + | *[[3D structures of human antibody|3D structures of human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Betacoronavirus england 1]] | + | [[Category: Betacoronavirus England 1]] |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Dimtrov, D S]] | + | [[Category: Large Structures]] |
| - | [[Category: Ying, T]] | + | [[Category: Dimtrov DS]] |
| - | [[Category: Zhou, T]] | + | [[Category: Ying T]] |
| - | [[Category: Antibody m336]] | + | [[Category: Zhou T]] |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Mers-cov rbd]]
| + | |
| - | [[Category: Neutralization]]
| + | |
| Structural highlights
Function
SPIKE_MERS1 Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Interacts with host DPP4 to mediate virla entry.[HAMAP-Rule:MF_04099][1] 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]
Publication Abstract from PubMed
The MERS-CoV is an emerging virus, which already infected more than 1,300 humans with high ( approximately 36%) mortality. Here, we show that m336, an exceptionally potent human anti-MERS-CoV antibody, is almost germline with only one somatic mutation in the heavy chain. The structure of Fab m336 in complex with the MERS-CoV receptor-binding domain reveals that its IGHV1-69-derived heavy chain provides more than 85% binding surface and that its epitope almost completely overlaps with the receptor-binding site. Analysis of antibodies from 69 healthy humans suggests an important role of the V(D)J recombination-generated junctional and allele-specific residues for achieving high affinity of binding at such low levels of somatic hypermutation. Our results also have important implications for development of vaccine immunogens based on the newly identified m336 epitope as well as for elucidation of mechanisms of neutralization by m336-like antibodies and their elicitation in vivo.
Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody.,Ying T, Prabakaran P, Du L, Shi W, Feng Y, Wang Y, Wang L, Li W, Jiang S, Dimitrov DS, Zhou T Nat Commun. 2015 Sep 15;6:8223. doi: 10.1038/ncomms9223. PMID:26370782[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Raj VS, Mou H, Smits SL, Dekkers DH, Muller MA, Dijkman R, Muth D, Demmers JA, Zaki A, Fouchier RA, Thiel V, Drosten C, Rottier PJ, Osterhaus AD, Bosch BJ, Haagmans BL. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature. 2013 Mar 14;495(7440):251-4. doi: 10.1038/nature12005. PMID:23486063 doi:http://dx.doi.org/10.1038/nature12005
- ↑ Ying T, Prabakaran P, Du L, Shi W, Feng Y, Wang Y, Wang L, Li W, Jiang S, Dimitrov DS, Zhou T. Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody. Nat Commun. 2015 Sep 15;6:8223. doi: 10.1038/ncomms9223. PMID:26370782 doi:http://dx.doi.org/10.1038/ncomms9223
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