OCA at 07:27, 3 May 2023

2023-05-03T07:27:53Z

← Older revision		Revision as of 07:27, 3 May 2023
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	~~'''Unreleased structure'''~~

	The ~~entry 8a96~~ is ~~ON HOLD~~		==SARS Cov2 Spike RBD in complex with Fab47==
			<StructureSection load='8a96' size='340' side='right'caption='[[8a96]], [[Resolution\|resolution]] 2.70Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[8a96]] 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 Severe acute respiratory syndrome coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8A96 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A96 FirstGlance]. <br>
			</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=8a96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a96 OCA], [https://pdbe.org/8a96 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a96 RCSB], [https://www.ebi.ac.uk/pdbsum/8a96 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a96 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 ==
			The human immunoglobulin heavy-chain (IGH) locus is exceptionally polymorphic, with high levels of allelic and structural variation. Thus, germline IGH genotypes are personal, which may influence responses to infection and vaccination. For an improved understanding of inter-individual differences in antibody responses, we isolated SARS-CoV-2 spike-specific monoclonal antibodies from convalescent health care workers, focusing on the IGHV1-69 gene, which has the highest level of allelic variation of all IGHV genes. The IGHV1-69( )20-using CAB-I47 antibody and two similar antibodies isolated from an independent donor were critically dependent on allele usage. Neutralization was retained when reverting the V region to the germline IGHV1-69( )20 allele but lost when reverting to other IGHV1-69 alleles. Structural data confirmed that two germline-encoded polymorphisms, R50 and F55, in the IGHV1-69 gene were required for high-affinity receptor-binding domain interaction. These results demonstrate that polymorphisms in IGH genes can influence the function of SARS-CoV-2 neutralizing antibodies.

	~~Authors:~~ Hallberg, B.M., ~~Das, H~~.		Immunoglobulin germline gene polymorphisms influence the function of SARS-CoV-2 neutralizing antibodies.,Pushparaj P, Nicoletto A, Sheward DJ, Das H, Castro Dopico X, Perez Vidakovics L, Hanke L, Chernyshev M, Narang S, Kim S, Fischbach J, Ekstrom S, McInerney G, Hallberg BM, Murrell B, Corcoran M, Karlsson Hedestam GB Immunity. 2023 Jan 10;56(1):193-206.e7. doi: 10.1016/j.immuni.2022.12.005. Epub , 2022 Dec 12. PMID:36574772<ref>PMID:36574772</ref>

	~~Description~~: ~~SARS Cov2 Spike RBD in complex with Fab47~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	[[Category: ~~Unreleased~~ Structures]]		</div>
	[[Category: Das, H]]		<div class="pdbe-citations 8a96" style="background-color:#fffaf0;"></div>
	[[Category: Hallberg~~, B.M~~]]		== References ==
			<references/>
			__TOC__
			</StructureSection>
			[[Category: Homo sapiens]]
			[[Category: Large Structures]]
			[[Category: Severe acute respiratory syndrome coronavirus]]
			[[Category: Das H]]
			[[Category: Hallberg BM]]

OCA: Protected "8a96" [edit=sysop:move=sysop]

2022-07-06T15:05:11Z

Protected "8a96" [edit=sysop:move=sysop]

← Older revision	Revision as of 15:05, 6 July 2022
(No difference)

OCA: New page: '''Unreleased structure''' The entry 8a96 is ON HOLD Authors: Hallberg, B.M., Das, H. Description: SARS Cov2 Spike RBD in complex with Fab47 Category: Unreleased Structures [[Categ...

2022-07-06T15:05:09Z

New page: '''Unreleased structure''' The entry 8a96 is ON HOLD Authors: Hallberg, B.M., Das, H. Description: SARS Cov2 Spike RBD in complex with Fab47 Category: Unreleased Structures [[Categ...

New page

'''Unreleased structure'''

The entry 8a96 is ON HOLD

Authors: Hallberg, B.M., Das, H.

Description: SARS Cov2 Spike RBD in complex with Fab47
[[Category: Unreleased Structures]]
[[Category: Das, H]]
[[Category: Hallberg, B.M]]

8a96 - Revision history

OCA at 07:27, 3 May 2023

OCA: Protected "8a96" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8a96 is ON HOLD Authors: Hallberg, B.M., Das, H. Description: SARS Cov2 Spike RBD in complex with Fab47 Category: Unreleased Structures [[Categ...