7c02
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
==Crystal structure of dimeric MERS-CoV receptor binding domain== | ==Crystal structure of dimeric MERS-CoV receptor binding domain== | ||
| - | <StructureSection load='7c02' size='340' side='right'caption='[[7c02]]' scene=''> | + | <StructureSection load='7c02' size='340' side='right'caption='[[7c02]], [[Resolution|resolution]] 2.91Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7C02 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7C02 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7c02]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mers Mers]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7C02 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7C02 FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7c02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c02 OCA], [http://pdbe.org/7c02 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7c02 RCSB], [http://www.ebi.ac.uk/pdbsum/7c02 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7c02 ProSAT]</span></td></tr> | + | </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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7c02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c02 OCA], [http://pdbe.org/7c02 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7c02 RCSB], [http://www.ebi.ac.uk/pdbsum/7c02 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7c02 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/A0A0A0Q7F3_9BETC A0A0A0Q7F3_9BETC]] 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;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Vaccines are urgently needed to control the ongoing pandemic COVID-19 and previously emerging MERS/SARS caused by coronavirus (CoV) infections. The CoV spike receptor-binding domain (RBD) is an attractive vaccine target but is undermined by limited immunogenicity. We describe a dimeric form of MERS-CoV RBD that overcomes this limitation. The RBD-dimer significantly increased neutralizing antibody (NAb) titers compared to conventional monomeric form and protected mice against MERS-CoV infection. Crystal structure showed RBD-dimer fully exposed dual receptor-binding motifs, the major target for NAbs. Structure-guided design further yielded a stable version of RBD-dimer as a tandem repeat single-chain (RBD-sc-dimer) which retained the vaccine potency. We generalized this strategy to design vaccines against COVID-19 and SARS, achieving 10- to 100-fold enhancement of NAb titers. RBD-sc-dimers in pilot scale production yielded high yields, supporting their scalability for further clinical development. The framework of immunogen design can be universally applied to other beta-CoV vaccines to counter emerging threats. | ||
| + | |||
| + | A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS.,Dai L, Zheng T, Xu K, Han Y, Xu L, Huang E, An Y, Cheng Y, Li S, Liu M, Yang M, Li Y, Cheng H, Yuan Y, Zhang W, Ke C, Wong G, Qi J, Qin C, Yan J, Gao GF Cell. 2020 Jun 28. pii: S0092-8674(20)30812-6. doi: 10.1016/j.cell.2020.06.035. PMID:32645327<ref>PMID:32645327</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7c02" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Dai L]] | + | [[Category: Mers]] |
| - | [[Category: Gao | + | [[Category: Dai, L]] |
| - | [[Category: Qi J]] | + | [[Category: Gao, G F]] |
| + | [[Category: Qi, J]] | ||
| + | [[Category: Mers-cov]] | ||
| + | [[Category: Receptor binding domain]] | ||
| + | [[Category: Vaccine]] | ||
| + | [[Category: Viral protein]] | ||
| + | [[Category: Virus]] | ||
Revision as of 11:39, 26 August 2020
Crystal structure of dimeric MERS-CoV receptor binding domain
| |||||||||||
Categories: Large Structures | Mers | Dai, L | Gao, G F | Qi, J | Mers-cov | Receptor binding domain | Vaccine | Viral protein | Virus
