7s3m: Difference between revisions
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==== | ==MERS-CoV S stem helix peptide bound to Fab22== | ||
<StructureSection load='7s3m' size='340' side='right'caption='[[7s3m]]' scene=''> | <StructureSection load='7s3m' size='340' side='right'caption='[[7s3m]], [[Resolution|resolution]] 2.40Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7s3m]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Middle_East_respiratory_syndrome-related_coronavirus Middle East respiratory syndrome-related coronavirus] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7S3M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7S3M FirstGlance]. <br> | ||
</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=7s3m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s3m OCA], [https://pdbe.org/7s3m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s3m RCSB], [https://www.ebi.ac.uk/pdbsum/7s3m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s3m ProSAT]</span></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]] 2.4Å</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=7s3m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s3m OCA], [https://pdbe.org/7s3m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s3m RCSB], [https://www.ebi.ac.uk/pdbsum/7s3m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s3m ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[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;"> | |||
== Publication Abstract from PubMed == | |||
Current coronavirus (CoV) vaccines primarily target immunodominant epitopes in the S1 subunit, which are poorly conserved and susceptible to escape mutations, thus threatening vaccine efficacy. Here, we use structure-guided protein engineering to remove the S1 subunit from the Middle East respiratory syndrome (MERS)-CoV spike (S) glycoprotein and develop stabilized stem (SS) antigens. Vaccination with MERS SS elicits cross-reactive beta-CoV antibody responses and protects mice against lethal MERS-CoV challenge. High-throughput screening of antibody-secreting cells from MERS SS-immunized mice led to the discovery of a panel of cross-reactive monoclonal antibodies. Among them, antibody IgG22 binds with high affinity to both MERS-CoV and severe acute respiratory syndrome (SARS)-CoV-2 S proteins, and a combination of electron microscopy and crystal structures localizes the epitope to a conserved coiled-coil region in the S2 subunit. Passive transfer of IgG22 protects mice against both MERS-CoV and SARS-CoV-2 challenge. Collectively, these results provide a proof of principle for cross-reactive CoV antibodies and inform the development of pan-CoV vaccines and therapeutic antibodies. | |||
Stabilized coronavirus spike stem elicits a broadly protective antibody.,Hsieh CL, Werner AP, Leist SR, Stevens LJ, Falconer E, Goldsmith JA, Chou CW, Abiona OM, West A, Westendorf K, Muthuraman K, Fritch EJ, Dinnon KH 3rd, Schafer A, Denison MR, Chappell JD, Baric RS, Graham BS, Corbett KS, McLellan JS Cell Rep. 2021 Nov 2;37(5):109929. doi: 10.1016/j.celrep.2021.109929. Epub 2021 , Oct 16. PMID:34710354<ref>PMID:34710354</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7s3m" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Middle East respiratory syndrome-related coronavirus]] | ||
[[Category: Mus musculus]] | |||
[[Category: Goldsmith JA]] | |||
[[Category: McLellan JS]] | |||