OCA at 06:35, 25 January 2023

OCA — Wed, 25 Jan 2023 06:35:19 GMT

←Older revision		Revision as of 06:35, 25 January 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8d48 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==sd1.040 Fab in complex with SARS-CoV-2 Spike 2P glycoprotein==
		+	<StructureSection load='8d48' size='340' side='right'caption='[[8d48]], [[Resolution\|resolution]] 3.70Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8d48]] 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=8D48 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8D48 FirstGlance]. <br>
		+	</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=8d48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8d48 OCA], [https://pdbe.org/8d48 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8d48 RCSB], [https://www.ebi.ac.uk/pdbsum/8d48 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8d48 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 ==
		+	Emergence of SARS-CoV-2 variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the four genera , including the nine human coronaviruses, through recognition of a conserved motif that includes the S2' site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization and, like fp.006 and hr2.016, protects mice when present as bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive with Orthocoronavirinae , including SARS-CoV-2 variants. ONE SENTENCE SUMMARY: Broadly cross-reactive antibodies that protect from SARS-CoV-2 variants are revealed by virus coldspot-driven discovery.

-	~~Authors~~:	+	Human neutralizing antibodies to cold linear epitopes and to subdomain 1 of SARS-CoV-2.,Bianchini F, Crivelli V, Abernathy ME, Guerra C, Palus M, Muri J, Marcotte H, Piralla A, Pedotti M, Gasparo R, Simonelli L, Matkovic M, Toscano C, Biggiogero M, Calvaruso V, Svoboda P, Rincon TC, Fava T, Podesvova L, Shanbhag AA, Celoria A, Sgrignani J, Stefanik M, Honig V, Pranclova V, Michalcikova T, Prochazka J, Guerrini G, Mehn D, Ciabattini A, Abolhassani H, Jarrossay D, Uguccioni M, Medaglini D, Pan-Hammarstrom Q, Calzolai L, Fernandez D, Baldanti F, Franzetti-Pellanda A, Garzoni C, Sedlacek R, Ruzek D, Varani L, Cavalli A, Barnes CO, Robbiani DF bioRxiv. 2022 Nov 28:2022.11.24.515932. doi: 10.1101/2022.11.24.515932. Preprint. PMID:36482967<ref>PMID:36482967</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8d48" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Severe acute respiratory syndrome coronavirus 2]]
		+	[[Category: Abernathy ME]]
		+	[[Category: Barnes CO]]

OCA at 15:10, 6 July 2022

OCA — Wed, 06 Jul 2022 15:10:04 GMT

←Older revision		Revision as of 15:10, 6 July 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8d48 is ON HOLD	+	The entry 8d48 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "8d48" [edit=sysop:move=sysop]

OCA — Wed, 08 Jun 2022 04:36:31 GMT

Protected "8d48" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:36, 8 June 2022

OCA: New page: '''Unreleased structure''' The entry 8d48 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 08 Jun 2022 04:36:30 GMT

New page: '''Unreleased structure''' The entry 8d48 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8d48 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

8d48 - Revision history

OCA at 06:35, 25 January 2023

OCA at 15:10, 6 July 2022

OCA: Protected "8d48" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8d48 is ON HOLD Authors: Description: Category: Unreleased Structures