3UJI

Crystal structure of anti-HIV-1 V3 Fab 2558 in complex with MN peptide

Summary for 3UJI

• Entry DOI: 10.2210/pdb3uji/pdb
• Related: 3UJJ
• Descriptor: Light chain of anti-HIV-1 V3 monoclonal antibody 2558, Fab region of the heavy chain of anti-HIV-1 V3 monoclonal antibody 2558, Envelope glycoprotein gp160, ... (6 entities in total)
• Functional Keywords: ig domains, antibody fab, antigen binding, the third variable region of hiv-1 gp120, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 49424.06

Authors

Kong, X.P. (deposition date: 2011-11-07, release date: 2011-12-28, Last modification date: 2024-11-27)

Primary citation

Gorny, M.K.,Sampson, J.,Li, H.,Jiang, X.,Totrov, M.,Wang, X.H.,Williams, C.,O'Neal, T.,Volsky, B.,Li, L.,Cardozo, T.,Nyambi, P.,Zolla-Pazner, S.,Kong, X.P.
Human Anti-V3 HIV-1 Monoclonal Antibodies Encoded by the VH5-51/VL Lambda Genes Define a Conserved Antigenic Structure.
Plos One, 6:e27780-e27780, 2011

PubMed Abstract: Preferential usage of immunoglobulin (Ig) genes that encode antibodies (Abs) against various pathogens is rarely observed and the nature of their dominance is unclear in the context of stochastic recombination of Ig genes. The hypothesis that restricted usage of Ig genes predetermines the antibody specificity was tested in this study of 18 human anti-V3 monoclonal Abs (mAbs) generated from unrelated individuals infected with various subtypes of HIV-1, all of which preferentially used pairing of the VH5-51 and VL lambda genes. Crystallographic analysis of five VH5-51/VL lambda-encoded Fabs complexed with various V3 peptides revealed a common three dimensional (3D) shape of the antigen-binding sites primarily determined by the four complementarity determining regions (CDR) for the heavy (H) and light (L) chains: specifically, the H1, H2, L1 and L2 domains. The CDR H3 domain did not contribute to the shape of the binding pocket, as it had different lengths, sequences and conformations for each mAb. The same shape of the binding site was further confirmed by the identical backbone conformation exhibited by V3 peptides in complex with Fabs which fully adapted to the binding pocket and the same key contact residues, mainly germline-encoded in the heavy and light chains of five Fabs. Finally, the VH5-51 anti-V3 mAbs recognized an epitope with an identical 3D structure which is mimicked by a single mimotope recognized by the majority of VH5-51-derived mAbs but not by other V3 mAbs. These data suggest that the identification of preferentially used Ig genes by neutralizing mAbs may define conserved epitopes in the diverse virus envelopes. This will be useful information for designing vaccine immunogen inducing cross-neutralizing Abs.

PubMed: 22164215
DOI: 10.1371/journal.pone.0027780

Experimental method

X-RAY DIFFRACTION (1.6 Å)