View source for 7sbu


==Crystal structure of SARS-CoV-2 spike protein receptor-binding domain in complex with a highly potent antibody J08 Fab==
<StructureSection load='7sbu' size='340' side='right'caption='[[7sbu]], [[Resolution|resolution]] 2.53&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7sbu]] is a 3 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=7SBU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SBU 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]] 2.53&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=7sbu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sbu OCA], [https://pdbe.org/7sbu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sbu RCSB], [https://www.ebi.ac.uk/pdbsum/7sbu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sbu ProSAT]</span></td></tr>
</table>
== Function ==
[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 ==
SignificanceClinical candidate monoclonal antibody J08 binds the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S-protein independent of known escape mutations and is able to potently neutralize most variants of concern (VoCs). Here, we explore these properties using cell-based assays and structural studies. A relatively small epitope footprint high on the receptor binding domain (RBD) ridge and the ability to bind multiple conformational states of the S-protein contribute to strong neutralization across several variants.

Structural insights of a highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody.,Torres JL, Ozorowski G, Andreano E, Liu H, Copps J, Piccini G, Donnici L, Conti M, Planchais C, Planas D, Manganaro N, Pantano E, Paciello I, Pileri P, Bruel T, Montomoli E, Mouquet H, Schwartz O, Sala C, De Francesco R, Wilson IA, Rappuoli R, Ward AB Proc Natl Acad Sci U S A. 2022 May 17;119(20):e2120976119. doi:, 10.1073/pnas.2120976119. Epub 2022 May 12. PMID:35549549<ref>PMID:35549549</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7sbu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Liu H]]
[[Category: Wilson IA]]