4OAW

Fab structure of anti-HIV gp120 V2 mAb 2158

Summary for 4OAW

• Entry DOI: 10.2210/pdb4oaw/pdb
• Descriptor: Light chain of Fab fragment of anti-HIV1 gp120 V2 mAb 2158, Heavy chain of Fab fragment of anti-HIV1 gp120 V2 mAb 2158, SULFATE ION, ... (5 entities in total)
• Functional Keywords: ig, antibody, hiv-1 gp120, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 97576.60

Authors

Spurrier, B.R.,Kong, X.P. (deposition date: 2014-01-06, release date: 2014-03-19, Last modification date: 2024-10-30)

Primary citation

Spurrier, B.,Sampson, J.,Gorny, M.K.,Zolla-Pazner, S.,Kong, X.P.
Functional Implications of the Binding Mode of a Human Conformation-Dependent V2 Monoclonal Antibody against HIV.
J.Virol., 88:4100-4112, 2014

PubMed Abstract: Data from the RV144 HIV vaccine trial indicated that gp120 V2 antibodies were associated with a lower risk of infection; thus, the mapping of V2 epitopes can contribute to the design of an effective HIV vaccine. We solved the crystal structure of human monoclonal antibody (MAb) 2158, which targets a conformational V2 epitope overlapping the α4β7 integrin binding site, and constructed a full-length model of V1V2. Comparison of computational energy stability to experimental enzyme-linked immunosorbent assay (ELISA) results identified a hydrophobic core that stabilizes the V2 region for optimal 2158 binding, as well as residues that directly mediate side chain interactions with MAb 2158. These data define the binding surface recognized by MAb 2158 and offer a structural explanation for why a mismatched mutation at position 181 (I181X) in the V2 loop was associated with a higher vaccine efficiency in the RV144 clinical vaccine trial.

PubMed: 24478429
DOI: 10.1128/JVI.03153-13

Experimental method

X-RAY DIFFRACTION (2.8 Å)