9MZ7

Crystal Structure of 19b Fab bound to the third variable (V3) loop peptide from the HIV-1 92BR020 envelope (Env) glycoprotein

Summary for 9MZ7

• Entry DOI: 10.2210/pdb9mz7/pdb
• Descriptor: 19b Fab Light Chain, 19b Fab Heavy Chain, 92BR020 Envelope glycoprotein, ... (6 entities in total)
• Functional Keywords: 19b, fab, fragment antigen-binding, hiv-1 envelope, immune system, immune system-viral protein complex, immune system/viral protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 51202.82

Authors

Fetics, S.,Acharya, P. (deposition date: 2025-01-22, release date: 2026-01-21, Last modification date: 2026-08-05)

Primary citation

Fetics, S.K.,Mehta, A.,Nicely, N.I.,Chen, C.-H.J.,Lindenberger, J.,Acharya, P.
Structural determination of the HIV-1 Variable Region 3 epitope of antibody 19b.
J.Virol., :e0213925-e0213925, 2026

PubMed Abstract: The HIV-1 Envelope (Env) in its pre-receptor "closed" conformation is targeted by broadly neutralizing antibodies (bnAbs), while its receptor-bound "open" conformation exposes immunodominant epitopes targeted by non-neutralizing antibodies. A human immunoglobulin G (IgG) monoclonal antibody (mAb), 19b, binds an Env third variable (V3) loop epitope that is only exposed in the open Env conformation. Despite widespread use of 19b to detect the open Env conformation in immunoassays, its epitope has not yet been structurally defined. Here, we determine crystal structures of ligand-free and V3 peptide-bound 19b Fab to visualize details of this interaction. 19b utilizes both its heavy and light chains to interact with the V3 loop. The 5-residue heavy-chain complementarity-determining region (CDR H3) forms a hydrophobic binding pocket to bind V3 residues. 19b adopts a cradle-binding mode, with its CDRH1, CDRL2, and CDRL3 mediating interactions with the V3 regions flanking the conserved GPGR/Q motif, while making only limited contacts with the GPGR arch region. Our high-resolution structures elucidate the epitope, binding mode, and the structural basis for the broad reactivity of 19b, thereby filling a gap in our knowledge of a widely used reagent in immunoassays.

PubMed: 42484331
DOI: 10.1128/jvi.02139-25

Experimental method

X-RAY DIFFRACTION (1.94 Å)