3GHE

Crystal structure of anti-HIV-1 Fab 537-10D in complex with V3 peptide MN

Summary for 3GHE

• Entry DOI: 10.2210/pdb3ghe/pdb
• Related: 1Q1J 3C2A 3GHB
• Descriptor: Fab 537-10D, light chain, Fab 537-10D, heavy chain, Envelope glycoprotein, ... (4 entities in total)
• Functional Keywords: hiv, v3 loop, antibody-antigen interactions, envelope protein, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 50092.72

Authors

Kong, X.P.,Burke, V.J. (deposition date: 2009-03-03, release date: 2009-12-01, Last modification date: 2024-04-03)

Primary citation

Burke, V.,Williams, C.,Sukumaran, M.,Kim, S.S.,Li, H.,Wang, X.H.,Gorny, M.K.,Zolla-Pazner, S.,Kong, X.P.
Structural basis of the cross-reactivity of genetically related human anti-HIV-1 mAbs: implications for design of V3-based immunogens
Structure, 17:1538-1546, 2009

PubMed Abstract: Human monoclonal antibodies 447-52D and 537-10D, both coded by the VH3 gene and specific for the third variable region (V3) of the HIV-1 gp120, were found to share antigen-binding structural elements including an elongated CDR H3 forming main-chain interactions with the N terminus of the V3 crown. However, water-mediated hydrogen bonds and a unique cation-pi sandwich stacking allow 447-52D to be broadly reactive with V3 containing both the GPGR and GPGQ crown motifs, while the deeper binding pocket and a buried Glu in the binding site of 537-10D limit its reactivity to only V3 containing the GPGR motif. Our results suggest that the design of immunogens for anti-V3 antibodies should avoid the Arg at the V3 crown, as GPGR-containing epitopes appear to select for B cells making antibodies of narrower specificity than V3 that carry Gln at this position.

PubMed: 19913488
DOI: 10.1016/j.str.2009.09.012

Experimental method

X-RAY DIFFRACTION (2.4 Å)