5v6l - Revision history

OCA at 13:42, 4 October 2023

OCA — Wed, 04 Oct 2023 13:42:43 GMT

←Older revision		Revision as of 13:42, 4 October 2023
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	<StructureSection load='5v6l' size='340' side='right'caption='[[5v6l]], [[Resolution\|resolution]] 2.55Å' scene=''>		<StructureSection load='5v6l' size='340' side='right'caption='[[5v6l]], [[Resolution\|resolution]] 2.55Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5v6l]] is a 6 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~European_rabbit European rabbit~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V6L OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5V6L FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5v6l]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] and [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V6L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5V6L FirstGlance]. <br>
-	</td></tr><tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat">[[~~5v6m~~\|~~5v6m~~]]</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]] 2.549Å</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=5v6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v6l OCA], [~~http~~://pdbe.org/5v6l PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5v6l RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5v6l PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5v6l 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=5v6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v6l OCA], [https://pdbe.org/5v6l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5v6l RCSB], [https://www.ebi.ac.uk/pdbsum/5v6l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5v6l ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/ENV_HV1JR ENV_HV1JR] The surface protein gp120 (SU) attaches the virus to the host lymphoid cell by binding to the primary receptor CD4. This interaction induces a structural rearrangement creating a high affinity binding site for a chemokine coreceptor like CXCR4 and/or CCR5. This peculiar 2 stage receptor-interaction strategy allows gp120 to maintain the highly conserved coreceptor-binding site in a cryptic conformation, protected from neutralizing antibodies. Since CD4 also displays a binding site for the disulfide-isomerase P4HB/PDI, a P4HB/PDI-CD4-CXCR4-gp120 complex may form. In that complex, P4HB/PDI could reach and reduce gp120 disulfide bonds, causing major conformational changes in gp120. TXN, another PDI family member could also be involved in disulfide rearrangements in Env during fusion. These changes are transmitted to the transmembrane protein gp41 and are thought to activate its fusogenic potential by unmasking its fusion peptide. Surface protein gp120 (SU) may target the virus to gut-associated lymphoid tissue (GALT) by binding host ITGA4/ITGB7 (alpha-4/beta-7 integrins), a complex that mediates T-cell migration to the GALT. Interaction between gp120 and ITGA4/ITGB7 would allow the virus to enter GALT early in the infection, infecting and killing most of GALT's resting CD4+ T-cells. This T-cell depletion is believed to be the major insult to the host immune system leading to AIDS (By similarity). The surface protein gp120 is a ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on endothelial cells of liver sinusoids and lymph node sinuses. These interactions allow capture of viral particles at mucosal surfaces by these cells and subsequent transmission to permissive cells. DCs are professional antigen presenting cells, critical for host immunity by inducing specific immune responses against a broad variety of pathogens. They act as sentinels in various tissues where they take up antigen, process it, and present it to T-cells following migration to lymphoid organs. HIV subverts the migration properties of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus transmission to permissive T-cells occurs either in trans (without DCs infection, through viral capture and transmission), or in cis (following DCs productive infection, through the usual CD4-gp120 interaction), thereby inducing a robust infection. In trans infection, bound virions remain infectious over days and it is proposed that they are not degraded, but protected in non-lysosomal acidic organelles within the DCs close to the cell membrane thus contributing to the viral infectious potential during DCs' migration from the periphery to the lymphoid tissues. On arrival at lymphoid tissues, intact virions recycle back to DCs' cell surface allowing virus transmission to CD4+ T-cells. Virion capture also seems to lead to MHC-II-restricted viral antigen presentation, and probably to the activation of HIV-specific CD4+ cells (By similarity). The transmembrane protein gp41 (TM) acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of viral and target intracellular membranes, 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. Complete fusion occurs in host cell endosomes and is dynamin-dependent, however some lipid transfer might occur at the plasma membrane. The virus undergoes clathrin-dependent internalization long before endosomal fusion, thus minimizing the surface exposure of conserved viral epitopes during fusion and reducing the efficacy of inhibitors targeting these epitopes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm (By similarity). The envelope glyprotein gp160 precursor down-modulates cell surface CD4 antigen by interacting with it in the endoplasmic reticulum and blocking its transport to the cell surface (By similarity). The gp120-gp41 heterodimer seems to contribute to T-cell depletion during HIV-1 infection. The envelope glycoproteins expressed on the surface of infected cells induce apoptosis through an interaction with uninfected cells expressing the receptor (CD4) and the coreceptors CXCR4 or CCR5. This type of bystander killing may be obtained by at least three distinct mechanisms. First, the interaction between the 2 cells can induce cellular fusion followed by nuclear fusion within the syncytium. Syncytia are condemned to die from apoptosis. Second, the 2 interacting cells may not fuse entirely and simply exchange plasma membrane lipids, after a sort of hemifusion process, followed by rapid death. Third, it is possible that virus-infected cells, on the point of undergoing apoptosis, fuse with CD4-expressing cells, in which case apoptosis is rapidly transmitted from one cell to the other and thus occurs in a sort of contagious fashion (By similarity). The gp120-gp41 heterodimer allows rapid transcytosis of the virus through CD4 negative cells such as simple epithelial monolayers of the intestinal, rectal and endocervical epithelial barriers. Both gp120 and gp41 specifically recognize glycosphingolipids galactosyl-ceramide (GalCer) or 3' sulfo-galactosyl-ceramide (GalS) present in the lipid rafts structures of epithelial cells. Binding to these alternative receptors allows the rapid transcytosis of the virus through the epithelial cells. This transcytotic vesicle-mediated transport of virions from the apical side to the basolateral side of the epithelial cells does not involve infection of the cells themselves (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~European rabbit~~]]	+	[[Category: Human immunodeficiency virus 1]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Kong, X P~~]]	+	[[Category: Oryctolagus cuniculus]]
-	[[Category: ~~Pan, R~~]]	+	[[Category: Kong X-P]]
-	[[Category: ~~Antibody]]~~	+	[[Category: Pan R]]
-	~~[[Category: Gp120]]~~	+
-	~~[[Category: Hiv]]~~	+
-	~~[[Category: V3]]~~	+
-	~~[[Category: Viral protein-immune system complex~~]]	+

OCA at 17:14, 11 December 2019

OCA — Wed, 11 Dec 2019 17:14:11 GMT

←Older revision		Revision as of 17:14, 11 December 2019
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	==Crystal Structure of Rabbit Anti-HIV-1 gp120 V3 Fab 10A37 in complex with V3 peptide JR-FL==		==Crystal Structure of Rabbit Anti-HIV-1 gp120 V3 Fab 10A37 in complex with V3 peptide JR-FL==
-	<StructureSection load='5v6l' size='340' side='right' caption='[[5v6l]], [[Resolution\|resolution]] 2.55Å' scene=''>	+	<StructureSection load='5v6l' size='340' side='right'caption='[[5v6l]], [[Resolution\|resolution]] 2.55Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5v6l]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V6L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V6L FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5v6l]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/European_rabbit European rabbit]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V6L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V6L FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5v6m\|5v6m]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5v6m\|5v6m]]</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=5v6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v6l OCA], [http://pdbe.org/5v6l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v6l RCSB], [http://www.ebi.ac.uk/pdbsum/5v6l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v6l ProSAT]</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=5v6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v6l OCA], [http://pdbe.org/5v6l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v6l RCSB], [http://www.ebi.ac.uk/pdbsum/5v6l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v6l ProSAT]</span></td></tr>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: European rabbit]]
		+	[[Category: Large Structures]]
	[[Category: Kong, X P]]		[[Category: Kong, X P]]
	[[Category: Pan, R]]		[[Category: Pan, R]]

OCA at 07:06, 31 January 2018

OCA — Wed, 31 Jan 2018 07:06:33 GMT

←Older revision		Revision as of 07:06, 31 January 2018
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	<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=5v6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v6l OCA], [http://pdbe.org/5v6l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v6l RCSB], [http://www.ebi.ac.uk/pdbsum/5v6l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v6l ProSAT]</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=5v6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v6l OCA], [http://pdbe.org/5v6l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v6l RCSB], [http://www.ebi.ac.uk/pdbsum/5v6l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v6l ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The V3 loop of HIV-1 gp120 is an immunodominant region targeted by neutralizing antibodies (nAbs). Despite limited breadth, better characterization of the structural details of the interactions between these nAbs and their target epitopes would enhance our understanding of the mechanism of neutralization and facilitate designing better immunogens to induce nAbs with greater breadth. Recently, we isolated two anti-V3 neutralizing monoclonal antibodies (mAbs), 10A3 and 10A37, from a rabbit immunized with gp120 of the M group consensus sequence. In this study, crystal structures of these mAbs bound to target epitopes were determined. 10A3 binds to the V3 crown ((303)TRKSIHIGPGRAF(317)), using the cradle binding mode similar to human V3 mAbs encoded by IGHV5-51 germline genes and its epitope structure resembles that bound to the human antibodies. In contrast, 10A37, which exhibits greater breadth and potency than 10A3, binds the V3 crown and the succeeding stem region ((308)HIGPGRAFYTTGEI(323)). Unexpectedly, the (315)RAFYTT(320) portion of the epitope existed as helical turns, a V3 structure that has not been observed previously. Its main chain-dominated antigen-antibody interactions not only explain the broad neutralization of 10A37 but also show that its epitope is a potential vaccine target to be further evaluated. In conclusion, our study provides novel insights about neutralization-susceptible epitope structures of the V3 loop of HIV-1 gp120 and demonstrates that, despite low amino acid sequence similarity from human antibody germline genes, rabbits can serve as a useful animal model to evaluate human vaccine candidates.IMPORTANCE The apex crown of the third variable loop (V3) of HIV-1 gp120 is the most immunogenic region of the surface glycoprotein and many mAbs targeting this region have been developed. Structural understanding of V3 crown mAbs not only can help understand how antibody responses targeting this unique region, but also contribute to immunogen design for vaccine development. We present here crystal structures of two neutralizing V3 mAbs, 10A3 and 10A37, developed from rabbits immunized with gp120. Our analysis of 10A3 in complex with V3 provided a detailed example of how epitope complexity can evolve with affinity maturation, while that of 10A37 revealed a novel V3 binding mode targeting the C-terminal side of V3 crown and showed that this region can form a helical structure. Our study provides novel insights about neutralization-susceptible V3 epitope structures and demonstrates that rabbits can serve as a useful animal model to evaluate human vaccine candidates.
		+
		+	Increased epitope complexity correlated with antibody affinity maturation and a novel binding mode revealed by structures of rabbit antibodies against the third variable loop (V3) of HIV-1 gp120.,Pan R, Qin Y, Banasik M, Lees W, Shepherd AJ, Cho MW, Kong XP J Virol. 2018 Jan 17. pii: JVI.01894-17. doi: 10.1128/JVI.01894-17. PMID:29343576<ref>PMID:29343576</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5v6l" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 06:53, 17 January 2018

OCA — Wed, 17 Jan 2018 06:53:00 GMT

←Older revision		Revision as of 06:53, 17 January 2018
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-	'''Unreleased structure'''

-	~~The entry 5v6l is ON HOLD until Paper Publication~~	+	==Crystal Structure of Rabbit Anti-HIV-1 gp120 V3 Fab 10A37 in complex with V3 peptide JR-FL==
-		+	<StructureSection load='5v6l' size='340' side='right' caption='[[5v6l]], [[Resolution\|resolution]] 2.55Å' scene=''>
-	~~Authors: Pan, R., Kong, X.-P.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5v6l]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V6L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V6L FirstGlance]. <br>
-	~~Description:~~ Crystal Structure of Rabbit Anti-HIV-1 gp120 V3 Fab 10A37 in complex with V3 peptide JR-FL	+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5v6m\|5v6m]]</td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	<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=5v6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v6l OCA], [http://pdbe.org/5v6l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v6l RCSB], [http://www.ebi.ac.uk/pdbsum/5v6l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v6l ProSAT]</span></td></tr>
-	[[Category: Kong, X.-P]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Kong, X P]]
	[[Category: Pan, R]]		[[Category: Pan, R]]
		+	[[Category: Antibody]]
		+	[[Category: Gp120]]
		+	[[Category: Hiv]]
		+	[[Category: V3]]
		+	[[Category: Viral protein-immune system complex]]

OCA at 06:59, 10 January 2018

OCA — Wed, 10 Jan 2018 06:59:40 GMT

←Older revision		Revision as of 06:59, 10 January 2018
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5v6l is ON HOLD	+	The entry 5v6l is ON HOLD until Paper Publication

	Authors: Pan, R., Kong, X.-P.		Authors: Pan, R., Kong, X.-P.

OCA at 04:48, 3 January 2018

OCA — Wed, 03 Jan 2018 04:48:03 GMT

←Older revision		Revision as of 04:48, 3 January 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5v6l is ON HOLD ~~until Paper Publication~~	+	The entry 5v6l is ON HOLD

	Authors: Pan, R., Kong, X.-P.		Authors: Pan, R., Kong, X.-P.
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	Description: Crystal Structure of Rabbit Anti-HIV-1 gp120 V3 Fab 10A37 in complex with V3 peptide JR-FL		Description: Crystal Structure of Rabbit Anti-HIV-1 gp120 V3 Fab 10A37 in complex with V3 peptide JR-FL
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Pan, R]]
	[[Category: Kong, X.-P]]		[[Category: Kong, X.-P]]
		+	[[Category: Pan, R]]

OCA at 13:54, 27 September 2017

OCA — Wed, 27 Sep 2017 13:54:52 GMT

←Older revision		Revision as of 13:54, 27 September 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5v6l is ON HOLD	+	The entry 5v6l is ON HOLD until Paper Publication

	Authors: Pan, R., Kong, X.-P.		Authors: Pan, R., Kong, X.-P.
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	Description: Crystal Structure of Rabbit Anti-HIV-1 gp120 V3 Fab 10A37 in complex with V3 peptide JR-FL		Description: Crystal Structure of Rabbit Anti-HIV-1 gp120 V3 Fab 10A37 in complex with V3 peptide JR-FL
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Kong, X.-P]]
	[[Category: Pan, R]]		[[Category: Pan, R]]
		+	[[Category: Kong, X.-P]]

OCA: Protected "5v6l" [edit=sysop:move=sysop]

OCA — Wed, 05 Apr 2017 11:40:03 GMT

Protected "5v6l" [edit=sysop:move=sysop]

←Older revision

Revision as of 11:40, 5 April 2017

OCA: New page: '''Unreleased structure''' The entry 5v6l is ON HOLD Authors: Pan, R., Kong, X.-P. Description: Crystal Structure of Rabbit Anti-HIV-1 gp120 V3 Fab 10A37 in complex with V3 peptide JR-...

OCA — Wed, 05 Apr 2017 11:40:01 GMT

New page: '''Unreleased structure''' The entry 5v6l is ON HOLD Authors: Pan, R., Kong, X.-P. Description: Crystal Structure of Rabbit Anti-HIV-1 gp120 V3 Fab 10A37 in complex with V3 peptide JR-...

New page

'''Unreleased structure'''

The entry 5v6l is ON HOLD

Authors: Pan, R., Kong, X.-P.

Description: Crystal Structure of Rabbit Anti-HIV-1 gp120 V3 Fab 10A37 in complex with V3 peptide JR-FL
[[Category: Unreleased Structures]]
[[Category: Kong, X.-P]]
[[Category: Pan, R]]