Details

Autor(en) / Beteiligte

• Bell, C.H.
• Pantophlet, R.
• Schiefner, A.
• Cavacini, L.A.
• Stanfield, R.L.
• Burton, D.R.
• Wilson, I.A.

Titel

Structure of Antibody F425-B4e8 in Complex With a V3 Peptide Reveals a New Binding Mode for Hiv-1 Neutralization

Ist Teil von

• Journal of molecular biology, 2009-05, Vol.375 (4)

Ort / Verlag

United States

Erscheinungsjahr

2009

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• 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.