OCA at 16:24, 18 October 2023

OCA — Wed, 18 Oct 2023 16:24:18 GMT

←Older revision		Revision as of 16:24, 18 October 2023
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-	====	+	==Crystal structure of SARS-CoV-2 receptor binding domain in complex with neutralizing human antibody WRAIR-2151.==
-	<StructureSection load='7n4m' size='340' side='right'caption='[[7n4m]]' scene=''>	+	<StructureSection load='7n4m' size='340' side='right'caption='[[7n4m]], [[Resolution\|resolution]] 3.79Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7n4m]] 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=7N4M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N4M 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=7n4m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n4m OCA], [https://pdbe.org/7n4m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n4m RCSB], [https://www.ebi.ac.uk/pdbsum/7n4m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n4m ProSAT]</span></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 3.79Å</td></tr>
		+	<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>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7n4m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n4m OCA], [https://pdbe.org/7n4m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n4m RCSB], [https://www.ebi.ac.uk/pdbsum/7n4m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n4m ProSAT]</span></td></tr>
	</table>		</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 ==
		+	Prevention of viral escape and increased coverage against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern require therapeutic monoclonal antibodies (mAbs) targeting multiple sites of vulnerability on the coronavirus spike glycoprotein. Here we identify several potent neutralizing antibodies directed against either the N-terminal domain (NTD) or the receptor-binding domain (RBD) of the spike protein. Administered in combinations, these mAbs provided low-dose protection against SARS-CoV-2 infection in the K18-human angiotensin-converting enzyme 2 mouse model, using both neutralization and Fc effector antibody functions. The RBD mAb WRAIR-2125, which targets residue F486 through a unique heavy-chain and light-chain pairing, demonstrated potent neutralizing activity against all major SARS-CoV-2 variants of concern. In combination with NTD and other RBD mAbs, WRAIR-2125 also prevented viral escape. These data demonstrate that NTD/RBD mAb combinations confer potent protection, likely leveraging complementary mechanisms of viral inactivation and clearance.
		+
		+	Low-dose in vivo protection and neutralization across SARS-CoV-2 variants by monoclonal antibody combinations.,Dussupt V, Sankhala RS, Mendez-Rivera L, Townsley SM, Schmidt F, Wieczorek L, Lal KG, Donofrio GC, Tran U, Jackson ND, Zaky WI, Zemil M, Tritsch SR, Chen WH, Martinez EJ, Ahmed A, Choe M, Chang WC, Hajduczki A, Jian N, Peterson CE, Rees PA, Rutkowska M, Slike BM, Selverian CN, Swafford I, Teng IT, Thomas PV, Zhou T, Smith CJ, Currier JR, Kwong PD, Rolland M, Davidson E, Doranz BJ, Mores CN, Hatziioannou T, Reiley WW, Bieniasz PD, Paquin-Proulx D, Gromowski GD, Polonis VR, Michael NL, Modjarrad K, Joyce MG, Krebs SJ Nat Immunol. 2021 Dec;22(12):1503-1514. doi: 10.1038/s41590-021-01068-z. Epub , 2021 Oct 29. PMID:34716452<ref>PMID:34716452</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7n4m" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Monoclonal Antibodies 3D structures\|Monoclonal Antibodies 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Severe acute respiratory syndrome coronavirus 2]]
		+	[[Category: Joyce MG]]
		+	[[Category: Sankhala RS]]

OCA at 06:15, 10 November 2021

OCA — Wed, 10 Nov 2021 06:15:45 GMT

←Older revision		Revision as of 06:15, 10 November 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7n4m ~~is ON HOLD~~	+	====
-		+	<StructureSection load='7n4m' size='340' side='right'caption='[[7n4m]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~:	+	</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=7n4m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n4m OCA], [https://pdbe.org/7n4m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n4m RCSB], [https://www.ebi.ac.uk/pdbsum/7n4m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n4m ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA: Protected "7n4m" [edit=sysop:move=sysop]

OCA — Wed, 09 Jun 2021 11:11:14 GMT

Protected "7n4m" [edit=sysop:move=sysop]

←Older revision

Revision as of 11:11, 9 June 2021

OCA: New page: '''Unreleased structure''' The entry 7n4m is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 09 Jun 2021 11:11:13 GMT

New page: '''Unreleased structure''' The entry 7n4m is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7n4m is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7n4m - Revision history

OCA at 16:24, 18 October 2023

OCA at 06:15, 10 November 2021

OCA: Protected "7n4m" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7n4m is ON HOLD Authors: Description: Category: Unreleased Structures