4llv - Revision history

OCA at 11:10, 14 December 2022

2022-12-14T11:10:02Z

←Older revision		Revision as of 11:10, 14 December 2022
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	<StructureSection load='4llv' size='340' side='right'caption='[[4llv]], [[Resolution\|resolution]] 2.39Å' scene=''>		<StructureSection load='4llv' size='340' side='right'caption='[[4llv]], [[Resolution\|resolution]] 2.39Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4llv]] is a 8 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LLV OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4LLV FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4llv]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LLV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LLV FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</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=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4llv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4llv OCA], [~~http~~://pdbe.org/4llv PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4llv RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4llv PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4llv ProSAT]</span></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=4llv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4llv OCA], [https://pdbe.org/4llv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4llv RCSB], [https://www.ebi.ac.uk/pdbsum/4llv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4llv ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 20:		Line 20:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Finton~~, K A.K~~]]	+	[[Category: Finton KAK]]
-	[[Category: Rupert~~, P B~~]]	+	[[Category: Rupert PB]]
-	[[Category: Strong~~, R K]]~~	+	[[Category: Strong RK]]
-	~~[[Category: Antibody]]~~	+
-	~~[[Category: Fv]]~~	+
-	~~[[Category: Hiv]]~~	+
-	~~[[Category: Immune system]]~~	+
-	~~[[Category: Immunoglobulin~~]]	+

OCA at 08:37, 3 April 2019

2019-04-03T08:37:15Z

←Older revision		Revision as of 08:37, 3 April 2019
Line 1:		Line 1:

	==The structure of the unbound form of anti-HIV antibody 4E10 Fv==		==The structure of the unbound form of anti-HIV antibody 4E10 Fv==
-	<StructureSection load='4llv' size='340' side='right' caption='[[4llv]], [[Resolution\|resolution]] 2.39Å' scene=''>	+	<StructureSection load='4llv' size='340' side='right'caption='[[4llv]], [[Resolution\|resolution]] 2.39Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4llv]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LLV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LLV FirstGlance]. <br>		<table><tr><td colspan='2'>[[4llv]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LLV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LLV FirstGlance]. <br>
Line 21:		Line 21:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Finton, K A.K]]		[[Category: Finton, K A.K]]
	[[Category: Rupert, P B]]		[[Category: Rupert, P B]]

OCA at 15:04, 11 August 2016

2016-08-11T15:04:09Z

←Older revision		Revision as of 15:04, 11 August 2016
Line 1:		Line 1:
		+
	==The structure of the unbound form of anti-HIV antibody 4E10 Fv==		==The structure of the unbound form of anti-HIV antibody 4E10 Fv==
	<StructureSection load='4llv' size='340' side='right' caption='[[4llv]], [[Resolution\|resolution]] 2.39Å' scene=''>		<StructureSection load='4llv' size='340' side='right' caption='[[4llv]], [[Resolution\|resolution]] 2.39Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4llv]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LLV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LLV FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4llv]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LLV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LLV FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4llv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4llv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4llv RCSB], [http://www.ebi.ac.uk/pdbsum/4llv PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4llv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4llv OCA], [http://pdbe.org/4llv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4llv RCSB], [http://www.ebi.ac.uk/pdbsum/4llv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4llv ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
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	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4llv" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Finton, K A.K]]		[[Category: Finton, K A.K]]
	[[Category: Rupert, P B]]		[[Category: Rupert, P B]]

OCA at 08:54, 20 January 2015

2015-01-20T08:54:30Z

←Older revision		Revision as of 08:54, 20 January 2015
Line 1:		Line 1:
-	~~{{STRUCTURE_4llv\| PDB=4llv \| SCENE= }}~~	+	==The structure of the unbound form of anti-HIV antibody 4E10 Fv==
-	===The structure of the unbound form of anti-HIV antibody 4E10 Fv===	+	<StructureSection load='4llv' size='340' side='right' caption='[[4llv]], [[Resolution\|resolution]] 2.39Å' scene=''>
-	~~{{ABSTRACT_PUBMED_24086134}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4llv]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LLV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LLV FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4llv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4llv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4llv RCSB], [http://www.ebi.ac.uk/pdbsum/4llv PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The broadly-neutralizing anti-HIV antibody 4E10 recognizes an epitope in the membrane-proximal external region of the HIV envelope protein gp41. Previous attempts to elicit 4E10 by vaccination with envelope-derived or reverse-engineered immunogens have failed. It was presumed that the ontogeny of 4E10-equivalent responses was blocked by inherent autoreactivity and exceptional polyreactivity. We generated 4E10 heavy-chain knock-in mice, which displayed significant B cell dysregulation, consistent with recognition of autoantigen/s by 4E10 and the presumption that tolerance mechanisms may hinder the elicitation of 4E10 or 4E10-equivalent responses. Previously proposed candidate 4E10 autoantigens include the mitochondrial lipid cardiolipin and a nuclear splicing factor, 3B3. However, using carefully-controlled assays, 4E10 bound only weakly to cardiolipin-containing liposomes, but also bound negatively-charged, non-cardiolipin-containing liposomes comparably poorly. 4E10/liposome binding was predominantly mediated by electrostatic interactions rather than presumed hydrophobic interactions. The crystal structure of 4E10 free of bound ligands showed a dramatic restructuring of the combining site, occluding the HIV epitope binding site and revealing profound flexibility, but creating an electropositive pocket consistent with non-specific binding of phospholipid headgroups. These results strongly suggested that antigens other than cardiolipin mediate 4E10 autoreactivity. Using a synthetic peptide library spanning the human proteome, we determined that 4E10 displays limited and focused, but unexceptional, polyspecificity. We also identified a novel autoepitope shared by three ER-resident inositol trisphosphate receptors, validated through binding studies and immunohistochemistry. Tissue staining with 4E10 demonstrated reactivity consistent with the type 1 inositol trisphosphate receptor as the most likely candidate autoantigen, but is inconsistent with splicing factor 3B3. These results demonstrate that 4E10 recognition of liposomes competes with MPER recognition and that HIV antigen and autoepitope recognition may be distinct enough to permit eliciting 4E10-like antibodies, evading autoimmunity through directed engineering. However, 4E10 combining site flexibility, exceptional for a highly-matured antibody, may preclude eliciting 4E10 by conventional immunization strategies.

-	~~==About this Structure==~~	+	Autoreactivity and Exceptional CDR Plasticity (but Not Unusual Polyspecificity) Hinder Elicitation of the Anti-HIV Antibody 4E10.,Finton KA, Larimore K, Larman HB, Friend D, Correnti C, Rupert PB, Elledge SJ, Greenberg PD, Strong RK PLoS Pathog. 2013 Sep;9(9):e1003639. Epub 2013 Sep 26. PMID:24086134<ref>PMID:24086134</ref>
-	~~[[4llv]] is a 8 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http~~:~~//oca~~.~~weizmann~~.~~ac.il~~/~~oca-bin/ocashort?id=4LLV OCA].~~	+

-	==~~Reference~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~<ref group="xtra">PMID:024086134</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	</div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Finton, K A.K.]]	+	[[Category: Finton, K A.K]]
-	[[Category: Rupert, P B.]]	+	[[Category: Rupert, P B]]
-	[[Category: Strong, R K~~.]]~~	+	[[Category: Strong, R K]]
-	~~[[Category: 4e10~~]]	+
	[[Category: Antibody]]		[[Category: Antibody]]
	[[Category: Fv]]		[[Category: Fv]]

OCA at 08:01, 16 October 2013

2013-10-16T08:01:38Z

←Older revision		Revision as of 08:01, 16 October 2013
Line 1:		Line 1:
-	~~'''Unreleased~~ structure~~'''~~	+	{{STRUCTURE_4llv\| PDB=4llv \| SCENE= }}
		+	===The structure of the unbound form of anti-HIV antibody 4E10 Fv===
		+	{{ABSTRACT_PUBMED_24086134}}

-	~~The entry~~ 4llv is ~~ON HOLD~~	+	==About this Structure==
		+	[[4llv]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LLV OCA].

-	~~Authors~~: Finton, K.A.K., Rupert, P.B., Strong, R.K.	+	==Reference==
-		+	<ref group="xtra">PMID:024086134</ref><references group="xtra"/><references/>
-	~~Description~~: ~~The structure of the unbound form of anti-HIV antibody 4E10~~ Fv	+	[[Category: Homo sapiens]]
		+	[[Category: Finton, K A.K.]]
		+	[[Category: Rupert, P B.]]
		+	[[Category: Strong, R K.]]
		+	[[Category: 4e10]]
		+	[[Category: Antibody]]
		+	[[Category: Fv]]
		+	[[Category: Hiv]]
		+	[[Category: Immune system]]
		+	[[Category: Immunoglobulin]]

OCA at 20:11, 7 August 2013

2013-08-07T20:11:29Z

←Older revision		Revision as of 20:11, 7 August 2013
Line 5:		Line 5:
	Authors: Finton, K.A.K., Rupert, P.B., Strong, R.K.		Authors: Finton, K.A.K., Rupert, P.B., Strong, R.K.

-	Description: ~~Autoreactivity and exceptional CDR plasticity (but not unusual polyspecificity) hinder elicitation~~ of the anti-HIV antibody 4E10	+	Description: The structure of the unbound form of anti-HIV antibody 4E10 Fv

OCA: Protected "4llv" [edit=sysop:move=sysop]

2013-07-18T04:48:03Z

Protected "4llv" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:48, 18 July 2013

OCA: New page: '''Unreleased structure''' The entry 4llv is ON HOLD Authors: Finton, K.A.K., Rupert, P.B., Strong, R.K. Description: Autoreactivity and exceptional CDR plasticity (but not unusual pol...

2013-07-18T04:48:02Z

New page: '''Unreleased structure''' The entry 4llv is ON HOLD Authors: Finton, K.A.K., Rupert, P.B., Strong, R.K. Description: Autoreactivity and exceptional CDR plasticity (but not unusual pol...

New page

'''Unreleased structure'''

The entry 4llv is ON HOLD

Authors: Finton, K.A.K., Rupert, P.B., Strong, R.K.

Description: Autoreactivity and exceptional CDR plasticity (but not unusual polyspecificity) hinder elicitation of the anti-HIV antibody 4E10