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4q2z

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Revision as of 17:15, 4 January 2017

Fab fragment of HIV vaccine-elicited CD4bs-directed antibody, GE356, from a non-human primate

Structural highlights

4q2z is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	4ktd, 4kte
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

Broadly neutralizing antibodies (bNAbs) isolated from chronically HIV-1 infected individuals reveal important information regarding how antibodies target conserved determinants of the envelope glycoprotein (Env) spike such as the primary receptor CD4 binding site (CD4bs). Many CD4bs-directed bNAbs use the same heavy (H) chain variable (V) gene segment, VH1-2*02, suggesting that activation of B cells expressing this allele is linked to the generation of this type of Ab. Here, we identify the rhesus macaque VH1.23 gene segment to be the closest macaque orthologue to the human VH1-2 gene segment, with 92% homology to VH1-2*02. Of the three amino acids in the VH1-2*02 gene segment that define a motif for VRC01-like antibodies (W50, N58, flanking the HCDR2 region, and R71), the two identified macaque VH1.23 alleles described here encode two. We demonstrate that immunization with soluble Env trimers induced CD4bs-specific VH1.23-using Abs with restricted neutralization breadth. Through alanine scanning and structural studies of one such monoclonal Ab (MAb), GE356, we demonstrate that all three HCDRs are involved in neutralization. This contrasts to the highly potent CD4bs-directed VRC01 class of bNAb, which bind Env predominantly through the HCDR2. Also unlike VRC01, GE356 was minimally modified by somatic hypermutation, its light (L) chain CDRs were of average lengths and it displayed a binding footprint proximal to the trimer axis. These results illustrate that the Env trimer immunogen used here activates B cells encoding a VH1-2 gene segment orthologue, but that the resulting Abs interact distinctly differently with the HIV-1 Env spike compared to VRC01.

HIV-1 receptor binding site-directed antibodies using a VH1-2 gene segment orthologue are activated by Env trimer immunization.,Navis M, Tran K, Bale S, Phad GE, Guenaga J, Wilson R, Soldemo M, McKee K, Sundling C, Mascola J, Li Y, Wyatt RT, Karlsson Hedestam GB PLoS Pathog. 2014 Aug 28;10(8):e1004337. doi: 10.1371/journal.ppat.1004337., eCollection 2014 Aug. PMID:25166308^[1]

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

References

↑ Navis M, Tran K, Bale S, Phad GE, Guenaga J, Wilson R, Soldemo M, McKee K, Sundling C, Mascola J, Li Y, Wyatt RT, Karlsson Hedestam GB. HIV-1 receptor binding site-directed antibodies using a VH1-2 gene segment orthologue are activated by Env trimer immunization. PLoS Pathog. 2014 Aug 28;10(8):e1004337. doi: 10.1371/journal.ppat.1004337., eCollection 2014 Aug. PMID:25166308 doi:http://dx.doi.org/10.1371/journal.ppat.1004337

1 Structural highlights
2 Publication Abstract from PubMed
3 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4q2z"

@@ Line 1: / Line 1: @@
 ==Fab fragment of HIV vaccine-elicited CD4bs-directed antibody, GE356, from a non-human primate==
 <StructureSection load='4q2z' size='340' side='right' caption='[[4q2z]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4q2z]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Q2Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Q2Z FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ktd|4ktd]], [[4kte|4kte]]</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=4q2z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q2z OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4q2z RCSB], [http://www.ebi.ac.uk/pdbsum/4q2z 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=4q2z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q2z OCA], [http://pdbe.org/4q2z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4q2z RCSB], [http://www.ebi.ac.uk/pdbsum/4q2z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4q2z ProSAT]</span></td></tr>
 </table>
 <div style="background-color:#fffaf0;">
@@ Line 14: / Line 15: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4q2z" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4q2z

From Proteopedia

Revision as of 17:15, 4 January 2017

Fab fragment of HIV vaccine-elicited CD4bs-directed antibody, GE356, from a non-human primate

Structural highlights

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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