4p9h

From Proteopedia

(Difference between revisions)

Revision as of 18:43, 4 August 2016

Crystal structure of 8ANC195 Fab in complex with gp120 of 93TH057 HIV-1 and soluble CD4 D1D2

Structural highlights

4p9h is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CD4_HUMAN] Accessory protein for MHC class-II antigen/T-cell receptor interaction. May regulate T-cell activation. Induces the aggregation of lipid rafts. [Q0ED31_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).

Publication Abstract from PubMed

Broadly neutralizing antibodies (bNAbs) to HIV-1 envelope glycoprotein (Env) can prevent infection in animal models. Characterized bNAb targets, although key to vaccine and therapeutic strategies, are currently limited. We defined a new site of vulnerability by solving structures of bNAb 8ANC195 complexed with monomeric gp120 by X-ray crystallography and trimeric Env by electron microscopy. The site includes portions of gp41 and N-linked glycans adjacent to the CD4-binding site on gp120, making 8ANC195 the first donor-derived anti-HIV-1 bNAb with an epitope spanning both Env subunits. Rather than penetrating the glycan shield by using a single variable-region CDR loop, 8ANC195 inserted its entire heavy-chain variable domain into a gap to form a large interface with gp120 glycans and regions of the gp120 inner domain not contacted by other bNAbs. By isolating additional 8ANC195 clonal variants, we identified a more potent variant, which may be valuable for therapeutic approaches using bNAb combinations with nonoverlapping epitopes.

Antibody 8ANC195 Reveals a Site of Broad Vulnerability on the HIV-1 Envelope Spike.,Scharf L, Scheid JF, Lee JH, West AP Jr, Chen C, Gao H, Gnanapragasam PN, Mares R, Seaman MS, Ward AB, Nussenzweig MC, Bjorkman PJ Cell Rep. 2014 May 8;7(3):785-95. doi: 10.1016/j.celrep.2014.04.001. Epub 2014, Apr 24. PMID:24767986^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Scharf L, Scheid JF, Lee JH, West AP Jr, Chen C, Gao H, Gnanapragasam PN, Mares R, Seaman MS, Ward AB, Nussenzweig MC, Bjorkman PJ. Antibody 8ANC195 Reveals a Site of Broad Vulnerability on the HIV-1 Envelope Spike. Cell Rep. 2014 May 8;7(3):785-95. doi: 10.1016/j.celrep.2014.04.001. Epub 2014, Apr 24. PMID:24767986 doi:http://dx.doi.org/10.1016/j.celrep.2014.04.001

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4p9h"

@@ Line 1: / Line 1: @@
 ==Crystal structure of 8ANC195 Fab in complex with gp120 of 93TH057 HIV-1 and soluble CD4 D1D2==
 <StructureSection load='4p9h' size='340' side='right' caption='[[4p9h]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4p9h]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P9H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P9H FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BAM:BENZAMIDINE'>BAM</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</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=4p9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p9h OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4p9h RCSB], [http://www.ebi.ac.uk/pdbsum/4p9h 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=4p9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p9h OCA], [http://pdbe.org/4p9h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4p9h RCSB], [http://www.ebi.ac.uk/pdbsum/4p9h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4p9h ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4p9h" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4p9h

From Proteopedia

Revision as of 18:43, 4 August 2016

Crystal structure of 8ANC195 Fab in complex with gp120 of 93TH057 HIV-1 and soluble CD4 D1D2

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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