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4yfl

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Revision as of 17:03, 22 March 2017

Crystal structure of VH1-46 germline-derived CD4-binding site-directed antibody 1B2530 in complex with HIV-1 clade A/E 93TH057 gp120

Structural highlights

4yfl is a 6 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

[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

The site on the HIV-1 gp120 glycoprotein that binds the CD4 receptor is recognized by broadly reactive antibodies, several of which neutralize over 90% of HIV-1 strains. To understand how antibodies achieve such neutralization, we isolated CD4-binding-site (CD4bs) antibodies and analyzed 16 co-crystal structures -8 determined here- of CD4bs antibodies from 14 donors. The 16 antibodies segregated by recognition mode and developmental ontogeny into two types: CDR H3-dominated and VH-gene-restricted. Both could achieve greater than 80% neutralization breadth, and both could develop in the same donor. Although paratope chemistries differed, all 16 gp120-CD4bs antibody complexes showed geometric similarity, with antibody-neutralization breadth correlating with antibody-angle of approach relative to the most effective antibody of each type. The repertoire for effective recognition of the CD4 supersite thus comprises antibodies with distinct paratopes arrayed about two optimal geometric orientations, one achieved by CDR H3 ontogenies and the other achieved by VH-gene-restricted ontogenies.

Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors.,Zhou T, Lynch RM, Chen L, Acharya P, Wu X, Doria-Rose NA, Joyce MG, Lingwood D, Soto C, Bailer RT, Ernandes MJ, Kong R, Longo NS, Louder MK, McKee K, O'Dell S, Schmidt SD, Tran L, Yang Z, Druz A, Luongo TS, Moquin S, Srivatsan S, Yang Y, Zhang B, Zheng A, Pancera M, Kirys T, Georgiev IS, Gindin T, Peng HP, Yang AS, Mullikin JC, Gray MD, Stamatatos L, Burton DR, Koff WC, Cohen MS, Haynes BF, Casazza JP, Connors M, Corti D, Lanzavecchia A, Sattentau QJ, Weiss RA, West AP Jr, Bjorkman PJ, Scheid JF, Nussenzweig MC, Shapiro L, Mascola JR, Kwong PD Cell. 2015 Jun 4;161(6):1280-92. doi: 10.1016/j.cell.2015.05.007. Epub 2015 May, 21. PMID:26004070^[1]

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

References

↑ Zhou T, Lynch RM, Chen L, Acharya P, Wu X, Doria-Rose NA, Joyce MG, Lingwood D, Soto C, Bailer RT, Ernandes MJ, Kong R, Longo NS, Louder MK, McKee K, O'Dell S, Schmidt SD, Tran L, Yang Z, Druz A, Luongo TS, Moquin S, Srivatsan S, Yang Y, Zhang B, Zheng A, Pancera M, Kirys T, Georgiev IS, Gindin T, Peng HP, Yang AS, Mullikin JC, Gray MD, Stamatatos L, Burton DR, Koff WC, Cohen MS, Haynes BF, Casazza JP, Connors M, Corti D, Lanzavecchia A, Sattentau QJ, Weiss RA, West AP Jr, Bjorkman PJ, Scheid JF, Nussenzweig MC, Shapiro L, Mascola JR, Kwong PD. Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors. Cell. 2015 Jun 4;161(6):1280-92. doi: 10.1016/j.cell.2015.05.007. Epub 2015 May, 21. PMID:26004070 doi:http://dx.doi.org/10.1016/j.cell.2015.05.007

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/4yfl"

@@ Line 1: / Line 1: @@
 ==Crystal structure of VH1-46 germline-derived CD4-binding site-directed antibody 1B2530 in complex with HIV-1 clade A/E 93TH057 gp120==
 <StructureSection load='4yfl' size='340' side='right' caption='[[4yfl]], [[Resolution|resolution]] 3.39&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4yfl]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YFL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YFL 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='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=4yfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yfl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4yfl RCSB], [http://www.ebi.ac.uk/pdbsum/4yfl 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=4yfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yfl OCA], [http://pdbe.org/4yfl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yfl RCSB], [http://www.ebi.ac.uk/pdbsum/4yfl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yfl 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 4yfl" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4yfl

From Proteopedia

Revision as of 17:03, 22 March 2017

Crystal structure of VH1-46 germline-derived CD4-binding site-directed antibody 1B2530 in complex with HIV-1 clade A/E 93TH057 gp120

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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