3hi1 - Revision history

OCA at 07:22, 6 September 2023

OCA — Wed, 06 Sep 2023 07:22:01 GMT

←Older revision		Revision as of 07:22, 6 September 2023
Line 3:		Line 3:
	<StructureSection load='3hi1' size='340' side='right'caption='[[3hi1]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='3hi1' size='340' side='right'caption='[[3hi1]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3hi1]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Hiv-1 Hiv-1~~] and [https://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HI1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HI1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3hi1]] 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_type_1_(isolate_YU2) Human immunodeficiency virus type 1 (isolate YU2)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HI1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HI1 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=NAG:N~~-~~ACETYL-D-GLUCOSAMINE'>NAG</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]] 2.9Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~env ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode~~=~~Info&srchmode~~=~~5&id=362651 HIV~~-~~1])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=3hi1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hi1 OCA], [https://pdbe.org/3hi1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hi1 RCSB], [https://www.ebi.ac.uk/pdbsum/3hi1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hi1 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=3hi1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hi1 OCA], [https://pdbe.org/3hi1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hi1 RCSB], [https://www.ebi.ac.uk/pdbsum/3hi1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hi1 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/ENV_HV1Y2 ENV_HV1Y2]] 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).	+	[https://www.uniprot.org/uniprot/ENV_HV1Y2 ENV_HV1Y2] 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).
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 36:		Line 36:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Hiv-1]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Arthos, J]]	+	[[Category: Arthos J]]
-	[[Category: Burton~~, D R~~]]	+	[[Category: Burton DR]]
-	[[Category: Cavacini, L]]	+	[[Category: Cavacini L]]
-	[[Category: Chen, L]]	+	[[Category: Chen L]]
-	~~[[Category: Dell, S O~~]]	+	[[Category: Dimitrov D]]
-	[[Category: Dimitrov, D]]	+	[[Category: Hessell AJ]]
-	[[Category: Hessell~~, A J~~]]	+	[[Category: Kwon YD]]
-	[[Category: Kwon~~, Y D~~]]	+	[[Category: Kwong PD]]
-	[[Category: Kwong~~, P D~~]]	+	[[Category: Mascola JR]]
-	[[Category: Mascola~~, J R~~]]	+	[[Category: Nabel GJ]]
-	[[Category: Nabel~~, G J~~]]	+	[[Category: O'Dell S]]
-	[[Category: Pancera, M]]	+	[[Category: Pancera M]]
-	[[Category: Posner, M]]	+	[[Category: Posner M]]
-	[[Category: Sodroski, J]]	+	[[Category: Sodroski J]]
-	[[Category: Tang, M]]	+	[[Category: Tang M]]
-	[[Category: Wu, X]]	+	[[Category: Wu X]]
-	[[Category: Wyatt, R]]	+	[[Category: Wyatt R]]
-	[[Category: Xu, L]]	+	[[Category: Xu L]]
-	[[Category: Yang, Z]]	+	[[Category: Yang Z]]
-	[[Category: Zhang, M Y]]	+	[[Category: Zhang M-Y]]
-	[[Category: Zhou, T]]	+	[[Category: Zhou T]]
-	~~[[Category: Aid]]~~	+
-	~~[[Category: Apoptosis]]~~	+
-	~~[[Category: Cd4 binding site antibody]]~~	+
-	~~[[Category: Cell membrane]]~~	+
-	~~[[Category: Cleavage on pair of basic residue]]~~	+
-	~~[[Category: Disulfide bond]]~~	+
-	~~[[Category: Envelope protein]]~~	+
-	~~[[Category: F105]]~~	+
-	~~[[Category: Fusion protein]]~~	+
-	~~[[Category: Glycoprotein]]~~	+
-	~~[[Category: Gp120]]~~	+
-	~~[[Category: Hiv]]~~	+
-	~~[[Category: Host-virus interaction]]~~	+
-	~~[[Category: Immune evasion]]~~	+
-	~~[[Category: Lipoprotein]]~~	+
-	~~[[Category: Membrane]]~~	+
-	~~[[Category: Palmitate]]~~	+
-	~~[[Category: Structural protein-immune system complex]]~~	+
-	~~[[Category: Transmembrane]]~~	+
-	~~[[Category: Viral immunoevasion]]~~	+
-	~~[[Category: Virion~~]]	+

OCA at 12:48, 23 March 2022

OCA — Wed, 23 Mar 2022 12:48:30 GMT

←Older revision		Revision as of 12:48, 23 March 2022
Line 1:		Line 1:

	==Structure of HIV-1 gp120 (core with V3) in Complex with CD4-Binding-Site Antibody F105==		==Structure of HIV-1 gp120 (core with V3) in Complex with CD4-Binding-Site Antibody F105==
-	<StructureSection load='3hi1' size='340' side='right' caption='[[3hi1]], [[Resolution\|resolution]] 2.90Å' scene=''>	+	<StructureSection load='3hi1' size='340' side='right'caption='[[3hi1]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3hi1]] is a 6 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Hiv-1 Hiv-1] and [~~http~~://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HI1 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3HI1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3hi1]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Hiv-1 Hiv-1] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HI1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HI1 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=362651 HIV-1])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">env ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=362651 HIV-1])</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=3hi1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hi1 OCA], [~~http~~://pdbe.org/3hi1 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3hi1 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3hi1 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3hi1 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=3hi1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hi1 OCA], [https://pdbe.org/3hi1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hi1 RCSB], [https://www.ebi.ac.uk/pdbsum/3hi1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hi1 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/ENV_HV1Y2 ENV_HV1Y2]] 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).	+	[[https://www.uniprot.org/uniprot/ENV_HV1Y2 ENV_HV1Y2]] 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).
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hi/3hi1_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hi/3hi1_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 29:		Line 29:
	</div>		</div>
	<div class="pdbe-citations 3hi1" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3hi1" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Gp120 3D structures\|Gp120 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 35:		Line 38:
	[[Category: Hiv-1]]		[[Category: Hiv-1]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
	[[Category: Arthos, J]]		[[Category: Arthos, J]]
	[[Category: Burton, D R]]		[[Category: Burton, D R]]

OCA at 21:49, 15 November 2017

OCA — Wed, 15 Nov 2017 21:49:46 GMT

←Older revision		Revision as of 21:49, 15 November 2017
Line 1:		Line 1:
		+
	==Structure of HIV-1 gp120 (core with V3) in Complex with CD4-Binding-Site Antibody F105==		==Structure of HIV-1 gp120 (core with V3) in Complex with CD4-Binding-Site Antibody F105==
	<StructureSection load='3hi1' size='340' side='right' caption='[[3hi1]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='3hi1' size='340' side='right' caption='[[3hi1]], [[Resolution\|resolution]] 2.90Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=362651 HIV-1])</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=362651 HIV-1])</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=3hi1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hi1 OCA], [http://pdbe.org/3hi1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hi1 RCSB], [http://www.ebi.ac.uk/pdbsum/3hi1 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=3hi1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hi1 OCA], [http://pdbe.org/3hi1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hi1 RCSB], [http://www.ebi.ac.uk/pdbsum/3hi1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3hi1 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 28:		Line 29:
	</div>		</div>
	<div class="pdbe-citations 3hi1" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3hi1" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Gp120\|Gp120]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 22:13, 8 February 2016

OCA — Mon, 08 Feb 2016 22:13:34 GMT

←Older revision		Revision as of 22:13, 8 February 2016
Line 2:		Line 2:
	<StructureSection load='3hi1' size='340' side='right' caption='[[3hi1]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='3hi1' size='340' side='right' caption='[[3hi1]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3hi1]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~] and [http://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=3HI1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HI1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3hi1]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Hiv-1 Hiv-1] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HI1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HI1 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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 Human immunodeficiency virus~~ 1])</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=362651 HIV-1])</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=3hi1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hi1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hi1 RCSB], [http://www.ebi.ac.uk/pdbsum/3hi1 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=3hi1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hi1 OCA], [http://pdbe.org/3hi1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hi1 RCSB], [http://www.ebi.ac.uk/pdbsum/3hi1 PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 17:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3hi1 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 27:		Line 27:
	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 3hi1" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 34:		Line 35:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Hiv-1]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Human immunodeficiency virus 1]]
	[[Category: Arthos, J]]		[[Category: Arthos, J]]
	[[Category: Burton, D R]]		[[Category: Burton, D R]]

OCA at 02:29, 25 December 2014

OCA — Thu, 25 Dec 2014 02:29:06 GMT

←Older revision		Revision as of 02:29, 25 December 2014
Line 7:		Line 7:
	<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=3hi1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hi1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hi1 RCSB], [http://www.ebi.ac.uk/pdbsum/3hi1 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=3hi1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hi1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hi1 RCSB], [http://www.ebi.ac.uk/pdbsum/3hi1 PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ENV_HV1Y2 ENV_HV1Y2]] 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).
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]

OCA at 06:18, 18 December 2014

OCA — Thu, 18 Dec 2014 06:18:23 GMT

←Older revision		Revision as of 06:18, 18 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3hi1\| PDB=3hi1 \| SCENE= }}~~	+	==Structure of HIV-1 gp120 (core with V3) in Complex with CD4-Binding-Site Antibody F105==
-	===Structure of HIV-1 gp120 (core with V3) in Complex with CD4-Binding-Site Antibody F105===	+	<StructureSection load='3hi1' size='340' side='right' caption='[[3hi1]], [[Resolution\|resolution]] 2.90Å' scene=''>
-	~~{{ABSTRACT_PUBMED_19965434}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3hi1]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://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=3HI1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HI1 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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 Human immunodeficiency virus 1])</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=3hi1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hi1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hi1 RCSB], [http://www.ebi.ac.uk/pdbsum/3hi1 PDBsum]</span></td></tr>
		+	</table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hi/3hi1_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The site on HIV-1 gp120 that binds to the CD4 receptor is vulnerable to antibodies. However, most antibodies that interact with this site cannot neutralize HIV-1. To understand the basis of this resistance, we determined co-crystal structures for two poorly neutralizing, CD4-binding site (CD4BS) antibodies, F105 and b13, in complexes with gp120. Both antibodies exhibited approach angles to gp120 similar to those of CD4 and a rare, broadly neutralizing CD4BS antibody, b12. Slight differences in recognition, however, resulted in substantial differences in F105- and b13-bound conformations relative to b12-bound gp120. Modeling and binding experiments revealed these conformations to be poorly compatible with the viral spike. This incompatibility, the consequence of slight differences in CD4BS recognition, renders HIV-1 resistant to all but the most accurately targeted antibodies.

-	~~==About this Structure==~~	+	Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120.,Chen L, Do Kwon Y, Zhou T, Wu X, O'Dell S, Cavacini L, Hessell AJ, Pancera M, Tang M, Xu L, Yang ZY, Zhang MY, Arthos J, Burton DR, Dimitrov DS, Nabel GJ, Posner MR, Sodroski J, Wyatt R, Mascola JR, Kwong PD Science. 2009 Nov 20;326(5956):1123-7. PMID:19965434<ref>PMID:19965434</ref>
-	~~[[3hi1]] is a 6 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens] and [http~~:~~//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=3HI1 OCA].~~	+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

	==See Also==		==See Also==
	*[[Gp120\|Gp120]]		*[[Gp120\|Gp120]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:019965434<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Human immunodeficiency virus 1]]		[[Category: Human immunodeficiency virus 1]]
-	[[Category: Arthos, J.]]	+	[[Category: Arthos, J]]
-	[[Category: Burton, D R.]]	+	[[Category: Burton, D R]]
-	[[Category: Cavacini, L.]]	+	[[Category: Cavacini, L]]
-	[[Category: Chen, L.]]	+	[[Category: Chen, L]]
-	[[Category: Dell, S O.]]	+	[[Category: Dell, S O]]
-	[[Category: Dimitrov, D.]]	+	[[Category: Dimitrov, D]]
-	[[Category: Hessell, A J.]]	+	[[Category: Hessell, A J]]
-	[[Category: Kwon, Y D.]]	+	[[Category: Kwon, Y D]]
-	[[Category: Kwong, P D.]]	+	[[Category: Kwong, P D]]
-	[[Category: Mascola, J R.]]	+	[[Category: Mascola, J R]]
-	[[Category: Nabel, G J.]]	+	[[Category: Nabel, G J]]
-	[[Category: Pancera, M.]]	+	[[Category: Pancera, M]]
-	[[Category: Posner, M.]]	+	[[Category: Posner, M]]
-	[[Category: Sodroski, J.]]	+	[[Category: Sodroski, J]]
-	[[Category: Tang, M.]]	+	[[Category: Tang, M]]
-	[[Category: Wu, X.]]	+	[[Category: Wu, X]]
-	[[Category: Wyatt, R.]]	+	[[Category: Wyatt, R]]
-	[[Category: Xu, L.]]	+	[[Category: Xu, L]]
-	[[Category: Yang, Z.]]	+	[[Category: Yang, Z]]
-	[[Category: Zhang, M Y.]]	+	[[Category: Zhang, M Y]]
-	[[Category: Zhou, T.]]	+	[[Category: Zhou, T]]
	[[Category: Aid]]		[[Category: Aid]]
	[[Category: Apoptosis]]		[[Category: Apoptosis]]

OCA: Protected "3hi1" [edit=sysop:move=sysop]

OCA — Mon, 11 Mar 2013 11:05:41 GMT

Protected "3hi1" [edit=sysop:move=sysop]

←Older revision

Revision as of 11:05, 11 March 2013

OCA at 11:05, 11 March 2013

OCA — Mon, 11 Mar 2013 11:05:38 GMT

←Older revision		Revision as of 11:05, 11 March 2013
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-	{{Seed}}
-	[[Image:3hi1.png\|left\|200px]]
-
-	<!--
-	The line below this paragraph, containing "STRUCTURE_3hi1", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3hi1\| PDB=3hi1 \| SCENE= }}		{{STRUCTURE_3hi1\| PDB=3hi1 \| SCENE= }}
-
	===Structure of HIV-1 gp120 (core with V3) in Complex with CD4-Binding-Site Antibody F105===		===Structure of HIV-1 gp120 (core with V3) in Complex with CD4-Binding-Site Antibody F105===
-
-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_19965434}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 19965434 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_19965434}}		{{ABSTRACT_PUBMED_19965434}}

	==About this Structure==		==About this Structure==
-	~~3HI1~~ is a 6 ~~chains~~ structure ~~of sequences~~ from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://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=3HI1 OCA].	+	[[3hi1]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://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=3HI1 OCA].
		+
		+	==See Also==
		+	*[[Gp120\|Gp120]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~19965434~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:019965434</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Human immunodeficiency virus 1]]		[[Category: Human immunodeficiency virus 1]]
Line 52:		Line 39:
	[[Category: Cell membrane]]		[[Category: Cell membrane]]
	[[Category: Cleavage on pair of basic residue]]		[[Category: Cleavage on pair of basic residue]]
-	[[Category: Coiled coil]]
	[[Category: Disulfide bond]]		[[Category: Disulfide bond]]
	[[Category: Envelope protein]]		[[Category: Envelope protein]]
Line 65:		Line 51:
	[[Category: Membrane]]		[[Category: Membrane]]
	[[Category: Palmitate]]		[[Category: Palmitate]]
-	[[Category: Structural protein/immune system complex]]	+	[[Category: Structural protein-immune system complex]]
	[[Category: Transmembrane]]		[[Category: Transmembrane]]
	[[Category: Viral immunoevasion]]		[[Category: Viral immunoevasion]]
	[[Category: Virion]]		[[Category: Virion]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Dec 30 14:24:07 2009''

OCA at 12:24, 30 December 2009

OCA — Wed, 30 Dec 2009 12:24:07 GMT

←Older revision		Revision as of 12:24, 30 December 2009
Line 1:		Line 1:
	{{Seed}}		{{Seed}}
-	[[Image:3hi1.~~jpg~~\|left\|200px]]	+	[[Image:3hi1.png\|left\|200px]]

	<!--		<!--
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	===Structure of HIV-1 gp120 (core with V3) in Complex with CD4-Binding-Site Antibody F105===		===Structure of HIV-1 gp120 (core with V3) in Complex with CD4-Binding-Site Antibody F105===

		+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_19965434}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 19965434 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_19965434}}

	==About this Structure==		==About this Structure==
	3HI1 is a 6 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://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=3HI1 OCA].		3HI1 is a 6 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://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=3HI1 OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:19965434</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Human immunodeficiency virus 1]]		[[Category: Human immunodeficiency virus 1]]
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	[[Category: Virion]]		[[Category: Virion]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Nov 18 20~~:06:16 2009''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Dec 30 14:24:07 2009''

OCA at 18:06, 18 November 2009

OCA — Wed, 18 Nov 2009 18:06:17 GMT

←Older revision		Revision as of 18:06, 18 November 2009
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{Seed}}
		+	[[Image:3hi1.jpg\|left\|200px]]

-	The ~~entry 3hi1~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3hi1", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3hi1\| PDB=3hi1 \| SCENE= }}

-	~~Authors: Kwon, Y.D., Chen, L., Zhou, T., Wu, X., O'Dell, S., Cavacini, L., Hessell, A.J., Pancera, M., Tang, M., Xu, L., Yang, Z., Zhang, M.~~-~~Y., Arthos, J., Burton, D.R., Dimitrov, D., Nabel, G.J., Posner, M., Sodroski, J., Wyatt, R., Mascola, J.R., Kwong, P.D.~~	+	===Structure of HIV-1 gp120 (core with V3) in Complex with CD4-Binding-Site Antibody F105===

-	Description: Structure of HIV-1 gp120 (core with V3) in Complex with CD4-Binding-Site Antibody F105

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Sep 23 08~~:27:37 2009''	+	==About this Structure==
		+	3HI1 is a 6 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://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=3HI1 OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Human immunodeficiency virus 1]]
		+	[[Category: Arthos, J.]]
		+	[[Category: Burton, D R.]]
		+	[[Category: Cavacini, L.]]
		+	[[Category: Chen, L.]]
		+	[[Category: Dell, S O.]]
		+	[[Category: Dimitrov, D.]]
		+	[[Category: Hessell, A J.]]
		+	[[Category: Kwon, Y D.]]
		+	[[Category: Kwong, P D.]]
		+	[[Category: Mascola, J R.]]
		+	[[Category: Nabel, G J.]]
		+	[[Category: Pancera, M.]]
		+	[[Category: Posner, M.]]
		+	[[Category: Sodroski, J.]]
		+	[[Category: Tang, M.]]
		+	[[Category: Wu, X.]]
		+	[[Category: Wyatt, R.]]
		+	[[Category: Xu, L.]]
		+	[[Category: Yang, Z.]]
		+	[[Category: Zhang, M Y.]]
		+	[[Category: Zhou, T.]]
		+	[[Category: Aid]]
		+	[[Category: Apoptosis]]
		+	[[Category: Cd4 binding site antibody]]
		+	[[Category: Cell membrane]]
		+	[[Category: Cleavage on pair of basic residue]]
		+	[[Category: Coiled coil]]
		+	[[Category: Disulfide bond]]
		+	[[Category: Envelope protein]]
		+	[[Category: F105]]
		+	[[Category: Fusion protein]]
		+	[[Category: Glycoprotein]]
		+	[[Category: Gp120]]
		+	[[Category: Hiv]]
		+	[[Category: Host-virus interaction]]
		+	[[Category: Immune evasion]]
		+	[[Category: Lipoprotein]]
		+	[[Category: Membrane]]
		+	[[Category: Palmitate]]
		+	[[Category: Structural protein/immune system complex]]
		+	[[Category: Transmembrane]]
		+	[[Category: Viral immunoevasion]]
		+	[[Category: Virion]]
		+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Nov 18 20:06:16 2009''