OCA at 12:41, 1 February 2024

OCA — Thu, 01 Feb 2024 12:41:05 GMT

←Older revision		Revision as of 12:41, 1 February 2024
Line 1:		Line 1:

-	====	+	==Crystal structure of the receptor binding domain of SARS-CoV-2 P.1 variant Spike glycoprotein in complex with COVOX-222 and EY6A Fabs==
-	<StructureSection load='7nxb' size='340' side='right'caption='[[7nxb]]' scene=''>	+	<StructureSection load='7nxb' size='340' side='right'caption='[[7nxb]], [[Resolution\|resolution]] 2.67Å' 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'>[[7nxb]] is a 5 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=7NXB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NXB 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=7nxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nxb OCA], [https://pdbe.org/7nxb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nxb RCSB], [https://www.ebi.ac.uk/pdbsum/7nxb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nxb 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]] 2.67Å</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>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7nxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nxb OCA], [https://pdbe.org/7nxb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nxb RCSB], [https://www.ebi.ac.uk/pdbsum/7nxb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nxb 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 ==
		+	Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations, including P.1 from Brazil, B.1.351 from South Africa, and B.1.1.7 from the UK (12, 10, and 9 changes in the spike, respectively). All have mutations in the ACE2 binding site, with P.1 and B.1.351 having a virtually identical triplet (E484K, K417N/T, and N501Y), which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine-induced antibody responses than B.1.351, suggesting that changes outside the receptor-binding domain (RBD) impact neutralization. Monoclonal antibody (mAb) 222 neutralizes all three variants despite interacting with two of the ACE2-binding site mutations. We explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.
		+
		+	Antibody evasion by the P.1 strain of SARS-CoV-2.,Dejnirattisai W, Zhou D, Supasa P, Liu C, Mentzer AJ, Ginn HM, Zhao Y, Duyvesteyn HME, Tuekprakhon A, Nutalai R, Wang B, Lopez-Camacho C, Slon-Campos J, Walter TS, Skelly D, Costa Clemens SA, Naveca FG, Nascimento V, Nascimento F, Fernandes da Costa C, Resende PC, Pauvolid-Correa A, Siqueira MM, Dold C, Levin R, Dong T, Pollard AJ, Knight JC, Crook D, Lambe T, Clutterbuck E, Bibi S, Flaxman A, Bittaye M, Belij-Rammerstorfer S, Gilbert SC, Carroll MW, Klenerman P, Barnes E, Dunachie SJ, Paterson NG, Williams MA, Hall DR, Hulswit RJG, Bowden TA, Fry EE, Mongkolsapaya J, Ren J, Stuart DI, Screaton GR Cell. 2021 May 27;184(11):2939-2954.e9. doi: 10.1016/j.cell.2021.03.055. Epub , 2021 Mar 30. PMID:33852911<ref>PMID:33852911</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7nxb" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Antibody 3D structures\|Antibody 3D structures]]
		+	*[[Monoclonal Antibodies 3D structures\|Monoclonal Antibodies 3D structures]]
		+	*[[Spike protein 3D structures\|Spike protein 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: Ren J]]
		+	[[Category: Stuart D]]
		+	[[Category: Zhou D]]

OCA at 06:56, 7 April 2021

OCA — Wed, 07 Apr 2021 06:56:09 GMT

←Older revision		Revision as of 06:56, 7 April 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7nxb ~~is ON HOLD~~	+	====
-		+	<StructureSection load='7nxb' size='340' side='right'caption='[[7nxb]]' scene=''>
-	~~Authors~~: ~~Zhou, D~~.~~, Ren, J~~.~~, Stuart, D~~.	+	== 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: Crystal structure of the receptor binding domain of SARS-CoV~~-~~2 P~~.~~1 variant Spike glycoprotein in complex with COVOX-222 and EY6A Fabs~~	+	</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=7nxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nxb OCA], [https://pdbe.org/7nxb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nxb RCSB], [https://www.ebi.ac.uk/pdbsum/7nxb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nxb ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Ren, J~~]]	+	__TOC__
-	[[Category: ~~Stuart, D~~]]	+	</StructureSection>
-	[[Category: ~~Zhou, D~~]]	+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

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

OCA — Wed, 24 Mar 2021 05:42:54 GMT

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

←Older revision

Revision as of 05:42, 24 March 2021

OCA: New page: '''Unreleased structure''' The entry 7nxb is ON HOLD Authors: Zhou, D., Ren, J., Stuart, D. Description: Crystal structure of the receptor binding domain of SARS-CoV-2 P.1 variant Spik...

OCA — Wed, 24 Mar 2021 05:42:53 GMT

New page: '''Unreleased structure''' The entry 7nxb is ON HOLD Authors: Zhou, D., Ren, J., Stuart, D. Description: Crystal structure of the receptor binding domain of SARS-CoV-2 P.1 variant Spik...

New page

'''Unreleased structure'''

The entry 7nxb is ON HOLD

Authors: Zhou, D., Ren, J., Stuart, D.

Description: Crystal structure of the receptor binding domain of SARS-CoV-2 P.1 variant Spike glycoprotein in complex with COVOX-222 and EY6A Fabs
[[Category: Unreleased Structures]]
[[Category: Ren, J]]
[[Category: Stuart, D]]
[[Category: Zhou, D]]

7nxb - Revision history

OCA at 12:41, 1 February 2024

OCA at 06:56, 7 April 2021

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

OCA: New page: '''Unreleased structure''' The entry 7nxb is ON HOLD Authors: Zhou, D., Ren, J., Stuart, D. Description: Crystal structure of the receptor binding domain of SARS-CoV-2 P.1 variant Spik...