View source for 6q06


==MERS-CoV S structure in complex with 2,3-sialyl-N-acetyl-lactosamine==
<SX load='6q06' size='340' side='right' viewer='molstar' caption='[[6q06]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6q06]] is a 3 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=6Q06 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Q06 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FOL:FOLIC+ACID'>FOL</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene></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=6q06 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q06 OCA], [https://pdbe.org/6q06 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6q06 RCSB], [https://www.ebi.ac.uk/pdbsum/6q06 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6q06 ProSAT]</span></td></tr>
</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]
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== Publication Abstract from PubMed ==
The Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and often lethal respiratory illness in humans, and no vaccines or specific treatments are available. Infections are initiated via binding of the MERS-CoV spike (S) glycoprotein to sialosides and dipeptidyl-peptidase 4 (the attachment and entry receptors, respectively). To understand MERS-CoV engagement of sialylated receptors, we determined the cryo-EM structures of S in complex with 5-N-acetyl neuraminic acid, 5-N-glycolyl neuraminic acid, sialyl-Lewis(X), alpha2,3-sialyl-N-acetyl-lactosamine and alpha2,6-sialyl-N-acetyl-lactosamine at 2.7-3.0 A resolution. We show that recognition occurs via a conserved groove that is essential for MERS-CoV S-mediated attachment to sialosides and entry into human airway epithelial cells. Our data illuminate MERS-CoV S sialoside specificity and suggest that selectivity for alpha2,3-linked over alpha2,6-linked receptors results from enhanced interactions with the former class of oligosaccharides. This study provides a structural framework explaining MERS-CoV attachment to sialoside receptors and identifies a site of potential vulnerability to inhibitors of viral entry.

Structures of MERS-CoV spike glycoprotein in complex with sialoside attachment receptors.,Park YJ, Walls AC, Wang Z, Sauer MM, Li W, Tortorici MA, Bosch BJ, DiMaio F, Veesler D Nat Struct Mol Biol. 2019 Dec;26(12):1151-1157. doi: 10.1038/s41594-019-0334-7., Epub 2019 Dec 2. PMID:31792450<ref>PMID:31792450</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6q06" style="background-color:#fffaf0;"></div>

==See Also==
*[[Sandbox 3001|Sandbox 3001]]
*[[Spike protein 3D structures|Spike protein 3D structures]]
== References ==
<references/>
__TOC__
</SX>
[[Category: Human betacoronavirus 2c EMC/2012]]
[[Category: Large Structures]]
[[Category: Bosch BJ]]
[[Category: DiMaio FD]]
[[Category: Li W]]
[[Category: Park YJ]]
[[Category: Sauer M]]
[[Category: Tortorici MA]]
[[Category: Veesler D]]
[[Category: Walls AC]]
[[Category: Wang Z]]