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| | ==Crystal structure of anti-HIV-1 V3 Fab 2557 in complex with an NOF V3 peptide== | | ==Crystal structure of anti-HIV-1 V3 Fab 2557 in complex with an NOF V3 peptide== |
| - | <StructureSection load='3mlv' size='340' side='right' caption='[[3mlv]], [[Resolution|resolution]] 2.48Å' scene=''> | + | <StructureSection load='3mlv' size='340' side='right'caption='[[3mlv]], [[Resolution|resolution]] 2.48Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3mlv]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv1 9hiv1] 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=3MLV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MLV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3mlv]] 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=3MLV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MLV FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3mlr|3mlr]], [[3mls|3mls]], [[3mlt|3mlt]], [[3mlu|3mlu]], [[3mlw|3mlw]], [[3mlx|3mlx]], [[3mly|3mly]], [[3mlz|3mlz]]</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]] 2.48Å</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=3mlv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mlv OCA], [http://pdbe.org/3mlv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3mlv RCSB], [http://www.ebi.ac.uk/pdbsum/3mlv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3mlv 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=3mlv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mlv OCA], [https://pdbe.org/3mlv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mlv RCSB], [https://www.ebi.ac.uk/pdbsum/3mlv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mlv ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/Q79790_9HIV1 Q79790_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.[SAAS:SAAS00139820] 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.[SAAS:SAAS00140087] | + | [https://www.uniprot.org/uniprot/Q79790_9HIV1 Q79790_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.[SAAS:SAAS00139820] 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.[SAAS:SAAS00140087] |
| | == 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/ml/3mlv_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ml/3mlv_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | ==See Also== | | ==See Also== |
| - | *[[3D structures of monoclonal antibody|3D structures of monoclonal antibody]] | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Kong, X P]] | + | [[Category: Human immunodeficiency virus 1]] |
| - | [[Category: Antibody-antigen interaction]] | + | [[Category: Large Structures]] |
| - | [[Category: Fab]] | + | [[Category: Kong X-P]] |
| - | [[Category: Gp120]]
| + | |
| - | [[Category: Hiv-1]]
| + | |
| - | [[Category: Human monoclonal antibody]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Third variable loop]]
| + | |
| Structural highlights
Function
Q79790_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.[SAAS:SAAS00139820] 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.[SAAS:SAAS00140087]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Binding of the third variable region (V3) of the HIV-1 envelope glycoprotein gp120 to the cell-surface coreceptors CCR5 or CXCR4 during viral entry suggests that there are conserved structural elements in this sequence-variable region. These conserved elements could serve as epitopes to be targeted by a vaccine against HIV-1. Here we perform a systematic structural analysis of representative human anti-V3 monoclonal antibodies in complex with V3 peptides, revealing that the crown of V3 has four conserved structural elements: an arch, a band, a hydrophobic core and the peptide backbone. These are either unaffected by or are subject to minimal sequence variation. As these regions are targeted by cross-clade neutralizing human antibodies, they provide a blueprint for the design of vaccine immunogens that could elicit broadly cross-reactive protective antibodies.
Conserved structural elements in the V3 crown of HIV-1 gp120.,Jiang X, Burke V, Totrov M, Williams C, Cardozo T, Gorny MK, Zolla-Pazner S, Kong XP Nat Struct Mol Biol. 2010 Aug;17(8):955-61. Epub 2010 Jul 11. PMID:20622876[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jiang X, Burke V, Totrov M, Williams C, Cardozo T, Gorny MK, Zolla-Pazner S, Kong XP. Conserved structural elements in the V3 crown of HIV-1 gp120. Nat Struct Mol Biol. 2010 Aug;17(8):955-61. Epub 2010 Jul 11. PMID:20622876 doi:10.1038/nsmb.1861
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