6w4m - Revision history

OCA at 14:16, 18 October 2023

2023-10-18T14:16:46Z

←Older revision		Revision as of 14:16, 18 October 2023
Line 1:		Line 1:

-	====	+	==CRYSTAL STRUCTURE OF THE ADCC-POTENT, WEAKLY NEUTRALIZING HIV ENV CO-RECEPTOR BINDING SITE ANTIBODY N12-I2 FAB IN COMPLEX WITH HIV-1 CLADE A/E GP120 AND M48U1==
-	<StructureSection load='6w4m' size='340' side='right'caption='[[6w4m]]' scene=''>	+	<StructureSection load='6w4m' size='340' side='right'caption='[[6w4m]], [[Resolution\|resolution]] 3.20Å' 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 [~~http~~://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6w4m]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5uwe 5uwe]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W4M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W4M FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6w4m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w4m OCA], [~~http~~://pdbe.org/6w4m PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6w4m RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6w4m PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6w4m 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]] 3.2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DPR:D-PROLINE'>DPR</scene>, <scene name='pdbligand=MPT:BETA-MERCAPTOPROPIONIC+ACID'>MPT</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene>, <scene name='pdbligand=U2X:O-(CYCLOHEXYLMETHYL)-L-TYROSINE'>U2X</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=6w4m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w4m OCA], [https://pdbe.org/6w4m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w4m RCSB], [https://www.ebi.ac.uk/pdbsum/6w4m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w4m ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/A0A0M3KKW9_9HIV1 A0A0M3KKW9_9HIV1]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	BACKGROUND: The binding of HIV-1 Envelope glycoproteins (Env) to host receptor CD4 exposes vulnerable conserved epitopes within the co-receptor binding site (CoRBS) which are required for the engagement of either CCR5 or CXCR4 co-receptor to allow HIV-1 entry. Antibodies against this region have been implicated in the protection against HIV acquisition in non-human primate (NHP) challenge studies and found to act synergistically with antibodies of other specificities to deliver effective Fc-mediated effector function against HIV-1-infected cells. Here, we describe the structure and function of N12-i2, an antibody isolated from an HIV-1-infected individual, and show how the unique structural features of this antibody allow for its effective Env recognition and Fc-mediated effector function. RESULTS: N12-i2 binds within the CoRBS utilizing two adjacent sulfo-tyrosines (TYS) for binding, one of which binds to a previously unknown TYS binding pocket formed by gp120 residues of high sequence conservation among HIV-1 strains. Structural alignment with gp120 in complex with the co-receptor CCR5 indicates that the new pocket corresponds to TYS at position 15 of CCR5. In addition, structure-function analysis of N12-i2 and other CoRBS-specific antibodies indicates a link between modes of antibody binding within the CoRBS and Fc-mediated effector activities. The efficiency of antibody-dependent cellular cytotoxicity (ADCC) correlated with both the level of antibody binding and the mode of antibody attachment to the epitope region, specifically with the way the Fc region was oriented relative to the target cell surface. Antibodies with poor Fc access mediated the poorest ADCC whereas those with their Fc region readily accessible for interaction with effector cells mediated the most potent ADCC. CONCLUSION: Our data identify a previously unknown binding site for TYS within the assembled CoRBS of the HIV-1 virus. In addition, our combined structural-modeling-functional analyses provide new insights into mechanisms of Fc-effector function of antibodies against HIV-1, in particular, how antibody binding to Env antigen affects the efficiency of ADCC response.
		+
		+	Defining rules governing recognition and Fc-mediated effector functions to the HIV-1 co-receptor binding site.,Tolbert WD, Sherburn R, Gohain N, Ding S, Flinko R, Orlandi C, Ray K, Finzi A, Lewis GK, Pazgier M BMC Biol. 2020 Jul 21;18(1):91. doi: 10.1186/s12915-020-00819-y. PMID:32693837<ref>PMID:32693837</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6w4m" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Antibody 3D structures\|Antibody 3D structures]]
		+	*[[Gp120 3D structures\|Gp120 3D structures]]
		+	*[[3D structures of human antibody\|3D structures of human antibody]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Human immunodeficiency virus 1]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Synthetic construct]]
		+	[[Category: Gohain N]]
		+	[[Category: Pazgier M]]
		+	[[Category: Tolbert WD]]

OCA at 05:30, 5 August 2020

2020-08-05T05:30:53Z

←Older revision		Revision as of 05:30, 5 August 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6w4m ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='6w4m' size='340' side='right'caption='[[6w4m]]' scene=''>
-	~~Authors~~: ~~Tolbert, W~~.D.~~, Gohain, N~~.~~, Pazgier, M~~.	+	== 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 [http://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~: ~~CRYSTAL STRUCTURE OF THE ADCC-POTENT~~, ~~WEAKLY NEUTRALIZING HIV ENV CO-RECEPTOR BINDING SITE ANTIBODY N12~~-~~I2 FAB IN COMPLEX WITH HIV-1 CLADE A~~/~~E GP120 AND M48U1~~	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6w4m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w4m OCA], [http://pdbe.org/6w4m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6w4m RCSB], [http://www.ebi.ac.uk/pdbsum/6w4m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6w4m ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Pazgier~~, M]]	+	__TOC__
-	[[Category: ~~Tolbert, W.D~~]]	+	</StructureSection>
-	[[Category: ~~Gohain, N~~]]	+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 08:22, 27 March 2020

2020-03-27T08:22:27Z

←Older revision		Revision as of 08:22, 27 March 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6w4m is ON HOLD	+	The entry 6w4m is ON HOLD until Paper Publication

	Authors: Tolbert, W.D., Gohain, N., Pazgier, M.		Authors: Tolbert, W.D., Gohain, N., Pazgier, M.
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	Description: CRYSTAL STRUCTURE OF THE ADCC-POTENT, WEAKLY NEUTRALIZING HIV ENV CO-RECEPTOR BINDING SITE ANTIBODY N12-I2 FAB IN COMPLEX WITH HIV-1 CLADE A/E GP120 AND M48U1		Description: CRYSTAL STRUCTURE OF THE ADCC-POTENT, WEAKLY NEUTRALIZING HIV ENV CO-RECEPTOR BINDING SITE ANTIBODY N12-I2 FAB IN COMPLEX WITH HIV-1 CLADE A/E GP120 AND M48U1
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Gohain, N]]
	[[Category: Pazgier, M]]		[[Category: Pazgier, M]]
	[[Category: Tolbert, W.D]]		[[Category: Tolbert, W.D]]
		+	[[Category: Gohain, N]]

OCA: Protected "6w4m" [edit=sysop:move=sysop]

2020-03-18T08:34:47Z

Protected "6w4m" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:34, 18 March 2020

OCA: New page: '''Unreleased structure''' The entry 6w4m is ON HOLD Authors: Tolbert, W.D., Gohain, N., Pazgier, M. Description: CRYSTAL STRUCTURE OF THE ADCC-POTENT, WEAKLY NEUTRALIZING HIV ENV CO-R...

2020-03-18T08:34:45Z

New page: '''Unreleased structure''' The entry 6w4m is ON HOLD Authors: Tolbert, W.D., Gohain, N., Pazgier, M. Description: CRYSTAL STRUCTURE OF THE ADCC-POTENT, WEAKLY NEUTRALIZING HIV ENV CO-R...

New page

'''Unreleased structure'''

The entry 6w4m is ON HOLD

Authors: Tolbert, W.D., Gohain, N., Pazgier, M.

Description: CRYSTAL STRUCTURE OF THE ADCC-POTENT, WEAKLY NEUTRALIZING HIV ENV CO-RECEPTOR BINDING SITE ANTIBODY N12-I2 FAB IN COMPLEX WITH HIV-1 CLADE A/E GP120 AND M48U1
[[Category: Unreleased Structures]]
[[Category: Gohain, N]]
[[Category: Pazgier, M]]
[[Category: Tolbert, W.D]]