5utf - Revision history

OCA at 13:34, 4 October 2023

2023-10-04T13:34:01Z

← Older revision		Revision as of 13:34, 4 October 2023
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	<StructureSection load='5utf' size='340' side='right'caption='[[5utf]], [[Resolution\|resolution]] 3.50Å' scene=''>		<StructureSection load='5utf' size='340' side='right'caption='[[5utf]], [[Resolution\|resolution]] 3.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5utf]] is a 6 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~9hiv1 9hiv1~~] and [~~http~~://en.wikipedia.org/wiki/Human ~~Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UTF OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5UTF FirstGlance]. <br>		<table><tr><td colspan='2'>[[5utf]] is a 6 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=5UTF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UTF FirstGlance]. <br>
	</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=~~NAG~~:~~N-ACETYL~~-D-~~GLUCOSAMINE~~'>~~NAG~~</scene>, <scene name='pdbligand=~~MAN~~:~~ALPHA~~-D-~~MANNOSE~~'>~~MAN~~</scene>~~</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]] 3.503Å</td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">env ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])~~</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'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5utf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5utf OCA], [~~http~~://pdbe.org/5utf PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5utf RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5utf PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5utf 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=5utf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5utf OCA], [https://pdbe.org/5utf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5utf RCSB], [https://www.ebi.ac.uk/pdbsum/5utf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5utf ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[~~[http~~://www.uniprot.org/uniprot/Q2N0S6_9HIV1 Q2N0S6_9HIV1]] 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).[RuleBase:RU004292][SAAS:SAAS000328_004_020447] 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).[SAAS:SAAS000328_004_240990]		[https://www.uniprot.org/uniprot/Q2N0S6_9HIV1 Q2N0S6_9HIV1] 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).[RuleBase:RU004292][SAAS:SAAS000328_004_020447] 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).[SAAS:SAAS000328_004_240990]
	<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: Human]]		[[Category: Homo sapiens]]
			[[Category: Human immunodeficiency virus 1]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Chuang, G Y]]		[[Category: Chuang G-Y]]
	[[Category: Kwong~~, P D~~]]		[[Category: Kwong PD]]
	[[Category: Pancera, M]]		[[Category: Pancera M]]
	[[Category: Xu, K]]		[[Category: Xu K]]
	~~[[Category: Hiv-1 env]]~~
	~~[[Category: Immune system]]~~
	~~[[Category: Near-native mimic of the viral spike]]~~
	~~[[Category: Stabilized env~~]]

OCA at 08:23, 30 September 2020

2020-09-30T08:23:26Z

← Older revision		Revision as of 08:23, 30 September 2020
Line 1:		Line 1:

	==Crystal Structure of a Stabilized DS-SOSIP.6mut BG505 gp140 HIV-1 Env Trimer, Containing Mutations I201C-P433C (DS), L154M, Y177W, N300M, N302M, T320L, I420M in Complex with Human Antibodies PGT122 and 35O22 at 4.3 A==		==Crystal Structure of a Stabilized DS-SOSIP.6mut BG505 gp140 HIV-1 Env Trimer, Containing Mutations I201C-P433C (DS), L154M, Y177W, N300M, N302M, T320L, I420M in Complex with Human Antibodies PGT122 and 35O22 at 4.3 A==
	<StructureSection load='5utf' size='340' side='right' caption='[[5utf]], [[Resolution\|resolution]] 3.50Å' scene=''>		<StructureSection load='5utf' size='340' side='right'caption='[[5utf]], [[Resolution\|resolution]] 3.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5utf]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UTF OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca.weizmann.ac~~.~~il/oca-docs~~/fgij/fg.htm?mol=5UTF FirstGlance]. <br>		<table><tr><td colspan='2'>[[5utf]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv1 9hiv1] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UTF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5UTF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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>		</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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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=5utf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5utf OCA], [http://pdbe.org/5utf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5utf RCSB], [http://www.ebi.ac.uk/pdbsum/5utf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5utf ProSAT]</span></td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">env ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</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=5utf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5utf OCA], [http://pdbe.org/5utf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5utf RCSB], [http://www.ebi.ac.uk/pdbsum/5utf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5utf ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5utf" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5utf" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Gp120 3D structures\|Gp120 3D structures]]
			*[[Gp41 3D Structures\|Gp41 3D Structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Chuang, G Y]]		[[Category: Chuang, G Y]]
	[[Category: Kwong, P D]]		[[Category: Kwong, P D]]

OCA at 14:05, 29 March 2017

2017-03-29T14:05:49Z

← Older revision		Revision as of 14:05, 29 March 2017
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

	The entry ~~5utf~~ is ~~ON HOLD~~		==Crystal Structure of a Stabilized DS-SOSIP.6mut BG505 gp140 HIV-1 Env Trimer, Containing Mutations I201C-P433C (DS), L154M, Y177W, N300M, N302M, T320L, I420M in Complex with Human Antibodies PGT122 and 35O22 at 4.3 A==
			<StructureSection load='5utf' size='340' side='right' caption='[[5utf]], [[Resolution\|resolution]] 3.50Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[5utf]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UTF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UTF FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5utf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5utf OCA], [http://pdbe.org/5utf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5utf RCSB], [http://www.ebi.ac.uk/pdbsum/5utf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5utf ProSAT]</span></td></tr>
			</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/Q2N0S6_9HIV1 Q2N0S6_9HIV1]] 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).[RuleBase:RU004292][SAAS:SAAS000328_004_020447] 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).[SAAS:SAAS000328_004_240990]
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The HIV-1-envelope (Env) trimer is a target for vaccine design as well as a conformational machine that facilitates virus entry by transitioning between prefusion-closed, CD4-bound, and co-receptor-bound conformations before rearranging into a postfusion state. Vaccine designers have sought to restrict the conformation of the HIV-1-Env trimer to its prefusion-closed state, as this state is recognized by most broadly neutralizing -but not by non-neutralizing- antibodies. We previously identified a disulfide bond, I201C-A433C (DS), which stabilizes Env in the vaccine-desired prefusion-closed state. When placed into the context of BG505 SOSIP.664, a soluble Env-trimer mimic developed by Sanders, Moore and colleagues, the engineered DS-SOSIP trimer showed reduced conformational triggering by CD4. Here, we further stabilize DS-SOSIP through a combination of structure-based design and 96-well-based expression and antigenic assessment. From 103 designs, we identified one, named DS-SOSIP.4mut, with four additional mutations at the interface of potentially mobile domains of the prefusion-closed structure. We also determined the crystal structures of DS-SOSIP.4mut at 4.1-A resolution - and of an additional DS-SOSIP.6mut variant at 4.3-A resolution - and these confirmed the formation of engineered disulfide bonds. Notably, DS-SOSIP.4mut elicited a higher ratio of tier-2 autologous titers versus tier-1 V3-sensitive titers as compared to BG505 SOSIP.664. DS-SOSIP.4mut also showed reduced recognition of CD4 and increased thermostability. The improved antigenicity, thermostability, and immunogenicity of DS-SOSIP.4mut suggests utility as an immunogen or a serologic probe; moreover, the specific 4mut alterations identified here, M154, M300, M302 and L320, can also be transferred to other HIV-1 Env trimers of interest to improve their properties.IMPORTANCE One approach to elicit broadly neutralizing antibodies against HIV-1 is to stabilize the structurally flexible HIV-1-envelope (Env) trimer in a conformation that displays predominantly broadly neutralizing epitopes, and few to no non-neutralizing epitopes. The prefusion-closed conformation of HIV-1 Env has been identified as one such preferred conformation, and a current leading vaccine candidate is the "BG505 DS-SOSIP" variant, comprising two disulfides and an Ile to Pro mutation of strain BG505. Here, we introduced additional mutations to further stabilize BG505 DS-SOSIP in the vaccine-preferred prefusion-closed conformation. In guinea pigs, our best mutant, DS-SOSIP.4mut, elicited a significantly higher ratio of autologous versus V3-directed neutralizing antibody responses than the SOSIP-stabilized form. We also observed an improvement in thermostability and a reduction in CD4 affinity. With improved antigenicity, stability, and immunogenicity, DS-SOSIP.4mut-stabilized trimers may have utility as HIV-1 immunogens, or in other antigen-specific contexts, such as with B-cell probes.

	~~Authors:~~ Pancera, M., ~~Chuang~~, G.-Y., Xu, K., Kwong~~, P~~.D.		Structure-Based Design of a Soluble Prefusion-Closed HIV-1-Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity.,Chuang GY, Geng H, Pancera M, Xu K, Cheng C, Acharya P, Chambers M, Druz A, Tsybovsky Y, Wanninger TG, Yang Y, Doria-Rose NA, Georgiev IS, Gorman J, Joyce MG, O'Dell S, Zhou T, McDermott AB, Mascola JR, Kwong PD J Virol. 2017 Mar 8. pii: JVI.02268-16. doi: 10.1128/JVI.02268-16. PMID:28275193<ref>PMID:28275193</ref>

	~~Description: Crystal Structure~~ of ~~a Stabilized DS-SOSIP~~.~~6mut BG505 gp140 HIV~~-~~1 Env trimer, Containing Mutations I201C~~-~~P433C (DS), L154M, Y177W, N300M, N302M, T320L, I420M in Complex with Human Antibodies PGT122 and 35O222 at 4.3 A~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[Category: Unreleased Structures]]~~		</div>
	[[Category: Chuang, G.-Y]]		<div class="pdbe-citations 5utf" style="background-color:#fffaf0;"></div>
	[[Category: Kwong, P.D]]		== References ==
			<references/>
			__TOC__
			</StructureSection>
			[[Category: Chuang, G Y]]
			[[Category: Kwong, P D]]
	[[Category: Pancera, M]]		[[Category: Pancera, M]]
	[[Category: Xu, K]]		[[Category: Xu, K]]
			[[Category: Hiv-1 env]]
			[[Category: Immune system]]
			[[Category: Near-native mimic of the viral spike]]
			[[Category: Stabilized env]]

OCA at 19:22, 15 March 2017

2017-03-15T19:22:11Z

← Older revision		Revision as of 19:22, 15 March 2017
Line 9:		Line 9:
	[[Category: Chuang, G.-Y]]		[[Category: Chuang, G.-Y]]
	[[Category: Kwong, P.D]]		[[Category: Kwong, P.D]]
			[[Category: Pancera, M]]
	[[Category: Xu, K]]		[[Category: Xu, K]]
	~~[[Category: Pancera, M]]~~

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

2017-03-09T14:54:17Z

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

← Older revision	Revision as of 14:54, 9 March 2017
(No difference)

OCA: New page: '''Unreleased structure''' The entry 5utf is ON HOLD Authors: Pancera, M., Chuang, G.-Y., Xu, K., Kwong, P.D. Description: Crystal Structure of a Stabilized DS-SOSIP.6mut BG505 gp140 H...

2017-03-09T14:54:14Z

New page: '''Unreleased structure''' The entry 5utf is ON HOLD Authors: Pancera, M., Chuang, G.-Y., Xu, K., Kwong, P.D. Description: Crystal Structure of a Stabilized DS-SOSIP.6mut BG505 gp140 H...

New page

'''Unreleased structure'''

The entry 5utf is ON HOLD

Authors: Pancera, M., Chuang, G.-Y., Xu, K., Kwong, P.D.

Description: Crystal Structure of a Stabilized DS-SOSIP.6mut BG505 gp140 HIV-1 Env trimer, Containing Mutations I201C-P433C (DS), L154M, Y177W, N300M, N302M, T320L, I420M in Complex with Human Antibodies PGT122 and 35O222 at 4.3 A
[[Category: Unreleased Structures]]
[[Category: Chuang, G.-Y]]
[[Category: Kwong, P.D]]
[[Category: Xu, K]]
[[Category: Pancera, M]]