8qpr: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8qpr is ON HOLD
+==SARS-CoV-2 S protein bound to human neutralising antibody UZGENT_G5==
+<StructureSection load='8qpr' size='340' side='right'caption='[[8qpr]], [[Resolution|resolution]] 3.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8qpr]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_virus_T4 Escherichia virus T4], [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=8QPR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8QPR 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]] 3.8&#8491;</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=8qpr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qpr OCA], [https://pdbe.org/8qpr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qpr RCSB], [https://www.ebi.ac.uk/pdbsum/8qpr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qpr ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/WAC_BPT4 WAC_BPT4] Chaperone responsible for attachment of long tail fibers to virus particle. Forms the fibrous structure on the neck of the virion called whiskers. During phage assembly, 6 fibritin molecules attach to each virion neck through their N-terminal domains, to form a collar with six fibers ('whiskers').[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]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+BACKGROUND: SARS-CoV-2-neutralizing antibodies (nABs) showed great promise in the early phases of the COVID-19 pandemic. The emergence of resistant strains, however, quickly rendered the majority of clinically approved nABs ineffective. This underscored the imperative to develop nAB cocktails targeting non-overlapping epitopes. METHODS: Undertaking a nAB discovery program, we employed a classical workflow, while integrating artificial intelligence (AI)-based prediction to select non-competing nABs very early in the pipeline. We identified and in vivo validated (in female Syrian hamsters) two highly potent nABs. FINDINGS: Despite the promising results, in depth cryo-EM structural analysis demonstrated that the AI-based prediction employed with the intention to ensure non-overlapping epitopes was inaccurate. The two nABs in fact bound to the same receptor-binding epitope in a remarkably similar manner. INTERPRETATION: Our findings indicate that, even in the Alphafold era, AI-based predictions of paratope-epitope interactions are rough and experimental validation of epitopes remains an essential cornerstone of a successful nAB lead selection. FUNDING: Full list of funders is provided at the end of the manuscript.
-Authors: Remaut, H., Reiter, D., Vandenkerckhove, L., Acar, D.D., Witkowski, W., Gerlo, S.
+Integrating artificial intelligence-based epitope prediction in a SARS-CoV-2 antibody discovery pipeline: caution is warranted.,Acar DD, Witkowski W, Wejda M, Wei R, Desmet T, Schepens B, De Cae S, Sedeyn K, Eeckhaut H, Fijalkowska D, Roose K, Vanmarcke S, Poupon A, Jochmans D, Zhang X, Abdelnabi R, Foo CS, Weynand B, Reiter D, Callewaert N, Remaut H, Neyts J, Saelens X, Gerlo S, Vandekerckhove L EBioMedicine. 2024 Feb;100:104960. doi: 10.1016/j.ebiom.2023.104960. Epub 2024 , Jan 16. PMID:38232633<ref>PMID:38232633</ref>
-Description: SARS-CoV-2 S protein bound to human neutralising antibody UZGENT_G5
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Witkowski, W]]
+<div class="pdbe-citations 8qpr" style="background-color:#fffaf0;"></div>
-[[Category: Vandenkerckhove, L]]
+== References ==
-[[Category: Gerlo, S]]
+<references/>
-[[Category: Reiter, D]]
+__TOC__
-[[Category: Remaut, H]]
+</StructureSection>
-[[Category: Acar, D.D]]
+[[Category: Escherichia virus T4]]
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Severe acute respiratory syndrome coronavirus 2]]
+[[Category: Acar DD]]
+[[Category: Gerlo S]]
+[[Category: Reiter D]]
+[[Category: Remaut H]]
+[[Category: Vandenkerckhove L]]
+[[Category: Witkowski W]]