7rks: Difference between revisions
New page: '''Unreleased structure''' The entry 7rks is ON HOLD Authors: Jette, C.A., Bjorkman, P.J., Barnes, C.O. Description: Structure of the SARS-CoV-2 receptor binding domain in complex with... |
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The | ==Structure of the SARS-CoV receptor binding domain in complex with the human neutralizing antibody Fab fragment, C118== | ||
<StructureSection load='7rks' size='340' side='right'caption='[[7rks]], [[Resolution|resolution]] 2.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7rks]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome-related_coronavirus Severe acute respiratory syndrome-related coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RKS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RKS FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <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'>[https://proteopedia.org/fgij/fg.htm?mol=7rks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rks OCA], [https://pdbe.org/7rks PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rks RCSB], [https://www.ebi.ac.uk/pdbsum/7rks PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rks ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/SPIKE_SARS SPIKE_SARS] May down-regulate host tetherin (BST2) by lysosomal degradation, thereby counteracting its antiviral activity.<ref>PMID:31199522</ref> Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 and CLEC4M/DC-SIGNR receptors and internalization of the virus into the endosomes of the host cell induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membrane fusion within endosomes.[HAMAP-Rule:MF_04099]<ref>PMID:14670965</ref> <ref>PMID:15496474</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]<ref>PMID:19321428</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Many anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) neutralizing antibodies target the angiotensin-converting enzyme 2 (ACE2) binding site on viral spike receptor-binding domains (RBDs). Potent antibodies recognize exposed variable epitopes, often rendering them ineffective against other sarbecoviruses and SARS-CoV-2 variants. Class 4 anti-RBD antibodies against a less-exposed, but more-conserved, cryptic epitope could recognize newly emergent zoonotic sarbecoviruses and variants, but they usually show only weak neutralization potencies. Here, we characterize two class 4 anti-RBD antibodies derived from coronavirus disease 2019 (COVID-19) donors that exhibit breadth and potent neutralization of zoonotic coronaviruses and SARS-CoV-2 variants. C118-RBD and C022-RBD structures reveal orientations that extend from the cryptic epitope to occlude ACE2 binding and CDRH3-RBD main-chain H-bond interactions that extend an RBD beta sheet, thus reducing sensitivity to RBD side-chain changes. A C118-spike trimer structure reveals rotated RBDs that allow access to the cryptic epitope and the potential for intra-spike crosslinking to increase avidity. These studies facilitate vaccine design and illustrate potential advantages of class 4 RBD-binding antibody therapeutics. | |||
Broad cross-reactivity across sarbecoviruses exhibited by a subset of COVID-19 donor-derived neutralizing antibodies.,Jette CA, Cohen AA, Gnanapragasam PNP, Muecksch F, Lee YE, Huey-Tubman KE, Schmidt F, Hatziioannou T, Bieniasz PD, Nussenzweig MC, West AP Jr, Keeffe JR, Bjorkman PJ, Barnes CO Cell Rep. 2021 Sep 28;36(13):109760. doi: 10.1016/j.celrep.2021.109760. Epub 2021 , Sep 8. PMID:34534459<ref>PMID:34534459</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Barnes | <div class="pdbe-citations 7rks" style="background-color:#fffaf0;"></div> | ||
[[Category: Bjorkman | |||
[[Category: Jette | ==See Also== | ||
*[[Spike protein 3D structures|Spike protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Severe acute respiratory syndrome-related coronavirus]] | |||
[[Category: Barnes CO]] | |||
[[Category: Bjorkman PJ]] | |||
[[Category: Jette CA]] | |||