7x7o: Difference between revisions
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The | ==SARS-CoV-2 spike RBD in complex with neutralizing antibody UT28K== | ||
<StructureSection load='7x7o' size='340' side='right'caption='[[7x7o]], [[Resolution|resolution]] 3.75Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7x7o]] is a 12 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=7X7O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7X7O 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]] 3.75Å</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=7x7o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7x7o OCA], [https://pdbe.org/7x7o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7x7o RCSB], [https://www.ebi.ac.uk/pdbsum/7x7o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7x7o 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 == | |||
Many potent neutralizing SARS-CoV-2 antibodies have been developed and used for therapies. However, the effectiveness of many antibodies has been reduced against recently emerging SARS-CoV-2 variants, especially the Omicron variant. We identified a highly potent SARS-CoV-2 neutralizing antibody, UT28K, in COVID-19 convalescent individuals who recovered from a severe condition. UT28K showed efficacy in neutralizing SARS-CoV-2 in an in vitro assay and in vivo prophylactic treatment, and the reactivity to the Omicron strain was reduced. The structural analyses revealed that antibody UT28K Fab and SARS-CoV-2 RBD protein interactions were mainly chain-dominated antigen-antibody interactions. In addition, a mutation analysis suggested that the emergence of a UT28K neutralization-resistant SARS-CoV-2 variant was unlikely, as this variant would likely lose its competitive advantage over circulating SARS-CoV-2. Our data suggest that UT28K offers potent protection against SARS-CoV-2, including newly emerging variants. | |||
Novel super-neutralizing antibody UT28K is capable of protecting against infection from a wide variety of SARS-CoV-2 variants.,Ozawa T, Tani H, Anraku Y, Kita S, Igarashi E, Saga Y, Inasaki N, Kawasuji H, Yamada H, Sasaki SI, Somekawa M, Sasaki J, Hayakawa Y, Yamamoto Y, Morinaga Y, Kurosawa N, Isobe M, Fukuhara H, Maenaka K, Hashiguchi T, Kishi H, Kitajima I, Saito S, Niimi H MAbs. 2022 Jan-Dec;14(1):2072455. doi: 10.1080/19420862.2022.2072455. PMID:35543180<ref>PMID:35543180</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7x7o" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Antibody 3D structures|Antibody 3D structures]] | ||
[[Category: | *[[Spike protein 3D structures|Spike protein 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: Kawasuji | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Severe acute respiratory syndrome coronavirus 2]] | ||
[[Category: | [[Category: Anraku Y]] | ||
[[Category: | [[Category: Fukuhara H]] | ||
[[Category: | [[Category: Hashiguchi T]] | ||
[[Category: | [[Category: Hayakawa Y]] | ||
[[Category: | [[Category: Igarashi E]] | ||
[[Category: | [[Category: Inasaki N]] | ||
[[Category: Saito | [[Category: Isobe M]] | ||
[[Category: | [[Category: Kawasuji H]] | ||
[[Category: | [[Category: Kishi H]] | ||
[[Category: | [[Category: Kita S]] | ||
[[Category: | [[Category: Kitajima I]] | ||
[[Category: | [[Category: Kurosawa N]] | ||
[[Category: Maenaka K]] | |||
[[Category: Morinaga Y]] | |||
[[Category: Niimi H]] | |||
[[Category: Ozawa T]] | |||
[[Category: Saga Y]] | |||
[[Category: Saito S]] | |||
[[Category: Sasaki J]] | |||
[[Category: Sasaki S]] | |||
[[Category: Somekawa M]] | |||
[[Category: Tani H]] | |||
[[Category: Yamada H]] | |||
[[Category: Yamamoto Y]] | |||