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| | <StructureSection load='4kqz' size='340' side='right'caption='[[4kqz]], [[Resolution|resolution]] 2.51Å' scene=''> | | <StructureSection load='4kqz' size='340' side='right'caption='[[4kqz]], [[Resolution|resolution]] 2.51Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4kqz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_betacoronavirus_2c_emc/2012 Human betacoronavirus 2c emc/2012]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KQZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KQZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4kqz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_betacoronavirus_2c_EMC/2012 Human betacoronavirus 2c EMC/2012]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KQZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KQZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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]] 2.514Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4kr0|4kr0]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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, spike ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1235996 Human betacoronavirus 2c EMC/2012])</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=4kqz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kqz OCA], [https://pdbe.org/4kqz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kqz RCSB], [https://www.ebi.ac.uk/pdbsum/4kqz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kqz 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=4kqz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kqz OCA], [http://pdbe.org/4kqz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kqz RCSB], [http://www.ebi.ac.uk/pdbsum/4kqz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kqz ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/K0BRG7_MERS K0BRG7_MERS] Spike protein S1: attaches the virion to the cell membrane by interacting with host receptor, initiating the infection.[HAMAP-Rule:MF_04099] Spike protein S2': Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099] Spike protein S2: 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] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4kqz" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4kqz" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Sandbox 3001|Sandbox 3001]] |
| | + | *[[Spike protein 3D structures|Spike protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human betacoronavirus 2c emc/2012]] | + | [[Category: Human betacoronavirus 2c EMC/2012]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bao, J]] | + | [[Category: Bao J]] |
| - | [[Category: Gao, F]] | + | [[Category: Gao F]] |
| - | [[Category: Gao, G F]] | + | [[Category: Gao GF]] |
| - | [[Category: Hu, Y]] | + | [[Category: Hu Y]] |
| - | [[Category: Li, Y]] | + | [[Category: Li Y]] |
| - | [[Category: Lu, G]] | + | [[Category: Lu G]] |
| - | [[Category: Qi, J]] | + | [[Category: Qi J]] |
| - | [[Category: Shi, Y]] | + | [[Category: Shi Y]] |
| - | [[Category: Wang, Q]] | + | [[Category: Wang Q]] |
| - | [[Category: Yan, J]] | + | [[Category: Yan J]] |
| - | [[Category: Yuan, Y]] | + | [[Category: Yuan Y]] |
| - | [[Category: Zhang, B]] | + | [[Category: Zhang B]] |
| - | [[Category: Zhang, W]] | + | [[Category: Zhang W]] |
| - | [[Category: Zhang, Y]] | + | [[Category: Zhang Y]] |
| - | [[Category: Cd26]]
| + | |
| - | [[Category: Core subdomain]]
| + | |
| - | [[Category: Receptor binding]]
| + | |
| - | [[Category: Strand-dominated receptor binding motif]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| - | [[Category: Viral surface]]
| + | |
| Structural highlights
Function
K0BRG7_MERS Spike protein S1: attaches the virion to the cell membrane by interacting with host receptor, initiating the infection.[HAMAP-Rule:MF_04099] Spike protein S2': Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099] Spike protein S2: 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]
Publication Abstract from PubMed
The newly emergent Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe pulmonary disease in humans, representing the second example of a highly pathogenic coronavirus, the first being SARS-CoV. CD26 (also known as dipeptidyl peptidase 4, DPP4) was recently identified as the cellular receptor for MERS-CoV. The engagement of the MERS-CoV spike protein with CD26 mediates viral attachment to host cells and virus-cell fusion, thereby initiating infection. Here we delineate the molecular basis of this specific interaction by presenting the first crystal structures of both the free receptor binding domain (RBD) of the MERS-CoV spike protein and its complex with CD26. Furthermore, binding between the RBD and CD26 is measured using real-time surface plasmon resonance with a dissociation constant of 16.7 nM. The viral RBD is composed of a core subdomain homologous to that of the SARS-CoV spike protein, and a unique strand-dominated external receptor binding motif that recognizes blades IV and V of the CD26 beta-propeller. The atomic details at the interface between the two binding entities reveal a surprising protein-protein contact mediated mainly by hydrophilic residues. Sequence alignment indicates, among betacoronaviruses, a possible structural conservation for the region homologous to the MERS-CoV RBD core, but a high variation in the external receptor binding motif region for virus-specific pathogenesis such as receptor recognition.
Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26.,Lu G, Hu Y, Wang Q, Qi J, Gao F, Li Y, Zhang Y, Zhang W, Yuan Y, Bao J, Zhang B, Shi Y, Yan J, Gao GF Nature. 2013 Aug 8;500(7461):227-31. doi: 10.1038/nature12328. Epub 2013 Jul 7. PMID:23831647[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lu G, Hu Y, Wang Q, Qi J, Gao F, Li Y, Zhang Y, Zhang W, Yuan Y, Bao J, Zhang B, Shi Y, Yan J, Gao GF. Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26. Nature. 2013 Aug 8;500(7461):227-31. doi: 10.1038/nature12328. Epub 2013 Jul 7. PMID:23831647 doi:http://dx.doi.org/10.1038/nature12328
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