7ucg - Revision history

OCA at 18:57, 7 September 2022

2022-09-07T18:57:54Z

←Older revision		Revision as of 18:57, 7 September 2022
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	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/Q202J5_9HIV1 Q202J5_9HIV1]] Envelope glycoprotein gp160: Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically cleaved in the trans-Golgi and thereby activated by cellular furin or furin-like proteases to produce gp120 and gp41.[HAMAP-Rule:MF_04083] Surface protein gp120: 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. Acts as 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. 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.[HAMAP-Rule:MF_04083] Transmembrane protein gp41: 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.[HAMAP-Rule:MF_04083]		[[https://www.uniprot.org/uniprot/Q202J5_9HIV1 Q202J5_9HIV1]] Envelope glycoprotein gp160: Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically cleaved in the trans-Golgi and thereby activated by cellular furin or furin-like proteases to produce gp120 and gp41.[HAMAP-Rule:MF_04083] Surface protein gp120: 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. Acts as 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. 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.[HAMAP-Rule:MF_04083] Transmembrane protein gp41: 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.[HAMAP-Rule:MF_04083]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The induction of broadly neutralizing antibodies (bNAbs) is a potential strategy for a vaccine against HIV-1. However, most bNAbs exhibit features such as unusually high somatic hypermutation, including insertions and deletions, which make their induction challenging. VRC01-class bNAbs not only exhibit extraordinary breadth and potency but also rank among the most highly somatically mutated bNAbs. Here, we describe a VRC01-class antibody isolated from a viremic controller, BG24, that is much less mutated than most relatives of its class while achieving comparable breadth and potency. A 3.8-A x-ray crystal structure of a BG24-BG505 Env trimer complex revealed conserved contacts at the gp120 interface characteristic of the VRC01-class Abs, despite lacking common CDR3 sequence motifs. The existence of moderately mutated CD4-binding site (CD4bs) bNAbs such as BG24 provides a simpler blueprint for CD4bs antibody induction by a vaccine, raising the prospect that such an induction might be feasible with a germline-targeting approach.
		+
		+	A naturally arising broad and potent CD4-binding site antibody with low somatic mutation.,Barnes CO, Schoofs T, Gnanapragasam PNP, Golijanin J, Huey-Tubman KE, Gruell H, Schommers P, Suh-Toma N, Lee YE, Cetrulo Lorenzi JC, Piechocka-Trocha A, Scheid JF, West AP Jr, Walker BD, Seaman MS, Klein F, Nussenzweig MC, Bjorkman PJ Sci Adv. 2022 Aug 12;8(32):eabp8155. doi: 10.1126/sciadv.abp8155. Epub 2022 Aug, 12. PMID:35960796<ref>PMID:35960796</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7ucg" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 16:49, 7 September 2022

2022-09-07T16:49:03Z

←Older revision		Revision as of 16:49, 7 September 2022
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-	==Structure of the ~~BG505~~ SOSIP.664 trimer in complex with neutralizing antibody Fab fragments 10-1074 and BG24==	+	==Structure of the DU422 SOSIP.664 trimer in complex with neutralizing antibody Fab fragments 10-1074 and BG24==
-	<StructureSection load='7ucg' size='340' side='right'caption='[[7ucg]]' scene=''>	+	<StructureSection load='7ucg' size='340' side='right'caption='[[7ucg]], [[Resolution\|resolution]] 3.50Å' 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=7UCG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UCG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7ucg]] is a 18 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UCG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UCG 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=7ucg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ucg OCA], [https://pdbe.org/7ucg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ucg RCSB], [https://www.ebi.ac.uk/pdbsum/7ucg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ucg ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <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=7ucg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ucg OCA], [https://pdbe.org/7ucg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ucg RCSB], [https://www.ebi.ac.uk/pdbsum/7ucg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ucg ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/Q202J5_9HIV1 Q202J5_9HIV1]] Envelope glycoprotein gp160: Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically cleaved in the trans-Golgi and thereby activated by cellular furin or furin-like proteases to produce gp120 and gp41.[HAMAP-Rule:MF_04083] Surface protein gp120: 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. Acts as 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. 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.[HAMAP-Rule:MF_04083] Transmembrane protein gp41: 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.[HAMAP-Rule:MF_04083]
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Human immunodeficiency virus 1]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Barnes CO]]		[[Category: Barnes CO]]
	[[Category: Bjorkman PJ]]		[[Category: Bjorkman PJ]]

OCA at 11:10, 31 August 2022

2022-08-31T11:10:52Z

←Older revision		Revision as of 11:10, 31 August 2022
Line 1:		Line 1:

-	====	+	==Structure of the BG505 SOSIP.664 trimer in complex with neutralizing antibody Fab fragments 10-1074 and BG24==
	<StructureSection load='7ucg' size='340' side='right'caption='[[7ucg]]' scene=''>		<StructureSection load='7ucg' size='340' side='right'caption='[[7ucg]]' 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'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UCG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UCG 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=7ucg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ucg OCA], [https://pdbe.org/7ucg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ucg RCSB], [https://www.ebi.ac.uk/pdbsum/7ucg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ucg ProSAT]</span></td></tr>		</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=7ucg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ucg OCA], [https://pdbe.org/7ucg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ucg RCSB], [https://www.ebi.ac.uk/pdbsum/7ucg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ucg ProSAT]</span></td></tr>
	</table>		</table>
Line 9:		Line 9:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Barnes CO]]
		+	[[Category: Bjorkman PJ]]

OCA at 06:20, 18 August 2022

2022-08-18T06:20:30Z

←Older revision		Revision as of 06:20, 18 August 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7ucg ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7ucg' size='340' side='right'caption='[[7ucg]]' scene=''>
-	~~Authors~~: ~~Barnes, C~~.O.~~, Bjorkman, P~~.J.	+	== 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~~: ~~Structure of the BG505 SOSIP~~.~~664 trimer in complex with neutralizing antibody Fab fragments 10~~-~~1074 and BG24~~	+	</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=7ucg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ucg OCA], [https://pdbe.org/7ucg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ucg RCSB], [https://www.ebi.ac.uk/pdbsum/7ucg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ucg ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[Category: ~~Barnes, C.O~~]]	+	__TOC__
-	[[Category: ~~Bjorkman, P.J~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 16:19, 27 July 2022

2022-07-27T16:19:32Z

←Older revision		Revision as of 16:19, 27 July 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7ucg is ON HOLD	+	The entry 7ucg is ON HOLD until Paper Publication

	Authors: Barnes, C.O., Bjorkman, P.J.		Authors: Barnes, C.O., Bjorkman, P.J.

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

2022-03-23T09:53:42Z

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

←Older revision

Revision as of 09:53, 23 March 2022

OCA: New page: '''Unreleased structure''' The entry 7ucg is ON HOLD Authors: Barnes, C.O., Bjorkman, P.J. Description: Structure of the BG505 SOSIP.664 trimer in complex with neutralizing antibody Fa...

2022-03-23T09:53:41Z

New page: '''Unreleased structure''' The entry 7ucg is ON HOLD Authors: Barnes, C.O., Bjorkman, P.J. Description: Structure of the BG505 SOSIP.664 trimer in complex with neutralizing antibody Fa...

New page

'''Unreleased structure'''

The entry 7ucg is ON HOLD

Authors: Barnes, C.O., Bjorkman, P.J.

Description: Structure of the BG505 SOSIP.664 trimer in complex with neutralizing antibody Fab fragments 10-1074 and BG24
[[Category: Unreleased Structures]]
[[Category: Barnes, C.O]]
[[Category: Bjorkman, P.J]]