2QSC

Crystal structure analysis of anti-HIV-1 V3-Fab F425-B4e8 in complex with a V3-peptide

Summary for 2QSC

• Entry DOI: 10.2210/pdb2qsc/pdb
• Descriptor: Fab F425-B4e8, Light chain, Fab F425-B4e8, Heavy chain, Envelope glycoprotein gp120, ... (7 entities in total)
• Functional Keywords: fab-peptide complex, hiv-1, gp120, v3 loop, immunoglobulin fold, aids, apoptosis, envelope protein, fusion protein, glycoprotein, host-virus interaction, membrane, transmembrane, viral immunoevasion, virion, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 49822.08

Authors

Bell, C.H.,Schiefner, A.,Stanfield, R.L.,Wilson, I.A. (deposition date: 2007-07-30, release date: 2008-01-15, Last modification date: 2024-11-06)

Primary citation

Bell, C.H.,Pantophlet, R.,Schiefner, A.,Cavacini, L.A.,Stanfield, R.L.,Burton, D.R.,Wilson, I.A.
Structure of antibody F425-B4e8 in complex with a V3 peptide reveals a new binding mode for HIV-1 neutralization.
J.Mol.Biol., 375:969-978, 2008

PubMed Abstract: F425-B4e8 (B4e8) is a monoclonal antibody isolated from a human immunodeficiency virus type 1 (HIV-1)-infected individual that recognizes the V3 variable loop on the gp120 subunit of the viral envelope spike. B4e8 neutralizes a subset of HIV-1 primary isolates from subtypes B, C and D, which places this antibody among the very few human anti-V3 antibodies with notable cross-neutralizing activity. Here, the crystal structure of the B4e8 Fab' fragment in complex with a 24-mer V3 peptide (RP142) at 2.8 A resolution is described. The complex structure reveals that the antibody recognizes a novel V3 loop conformation, featuring a five-residue alpha-turn around the conserved GPGRA apex of the beta-hairpin loop. In agreement with previous mutagenesis analyses, the Fab' interacts primarily with V3 through side-chain contacts with just two residues, Ile(P309) and Arg(P315), while the remaining contacts are to the main chain. The structure helps explain how B4e8 can tolerate a certain degree of sequence variation within V3 and, hence, is able to neutralize an appreciable number of different HIV-1 isolates.

PubMed: 18068724
DOI: 10.1016/j.jmb.2007.11.013

Experimental method

X-RAY DIFFRACTION (2.8 Å)