8gf2

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m (Protected "8gf2" [edit=sysop:move=sysop])
Current revision (05:53, 23 August 2023) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 8gf2 is ON HOLD until Paper Publication
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==Crystal structure of SARS-CoV-2 receptor binding domain in complex with antibodies eCR3022.20 and CC12.3==
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<StructureSection load='8gf2' size='340' side='right'caption='[[8gf2]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8gf2]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8GF2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GF2 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.851&#8491;</td></tr>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8gf2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gf2 OCA], [https://pdbe.org/8gf2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gf2 RCSB], [https://www.ebi.ac.uk/pdbsum/8gf2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gf2 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/SPIKE_SARS2 SPIKE_SARS2] attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 receptor and internalization of the virus into the endosomes of the host cell induces conformational changes in the Spike glycoprotein (PubMed:32142651, PubMed:32075877, PubMed:32155444). Uses also human TMPRSS2 for priming in human lung cells which is an essential step for viral entry (PubMed:32142651). Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes.[HAMAP-Rule:MF_04099]<ref>PMID:32075877</ref> <ref>PMID:32142651</ref> <ref>PMID:32155444</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]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for strategies to rapidly develop neutralizing monoclonal antibodies that can function as prophylactic and therapeutic agents and to help guide vaccine design. Here, we demonstrate that engineering approaches can be used to refocus an existing antibody that neutralizes one virus but not a related virus. Through a rapid affinity maturation strategy, we engineered CR3022, a SARS-CoV-1-neutralizing antibody, to bind to the receptor binding domain of SARS-CoV-2 with &gt;1000-fold increased affinity. The engineered CR3022 neutralized SARS-CoV-2 and provided prophylactic protection from viral challenge in a small animal model of SARS-CoV-2 infection. Deep sequencing throughout the engineering process paired with crystallographic analysis of engineered CR3022 elucidated the molecular mechanisms by which the antibody can accommodate sequence differences in the epitopes between SARS-CoV-1 and SARS-CoV-2. This workflow provides a blueprint for the rapid broadening of neutralization of an antibody from one virus to closely related but resistant viruses.
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Authors:
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Broadening a SARS-CoV-1-neutralizing antibody for potent SARS-CoV-2 neutralization through directed evolution.,Zhao F, Yuan M, Keating C, Shaabani N, Limbo O, Joyce C, Woehl J, Barman S, Burns A, Tran Q, Zhu X, Ricciardi M, Peng L, Smith J, Huang D, Briney B, Sok D, Nemazee D, Teijaro JR, Wilson IA, Burton DR, Jardine JG Sci Signal. 2023 Aug 15;16(798):eabk3516. doi: 10.1126/scisignal.abk3516. Epub , 2023 Aug 15. PMID:37582161<ref>PMID:37582161</ref>
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Description:
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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<div class="pdbe-citations 8gf2" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Severe acute respiratory syndrome coronavirus 2]]
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[[Category: Wilson IA]]
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[[Category: Yuan M]]
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[[Category: Zhu X]]

Current revision

Crystal structure of SARS-CoV-2 receptor binding domain in complex with antibodies eCR3022.20 and CC12.3

PDB ID 8gf2

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