2QSC: Crystal Structure Analysis Of Anti-Hiv-1 V3-Fab F425-B4e8 In Complex With A V3-Peptide

Citation:
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.
PDB ID: 2QSCDownload
MMDB ID: 61803
PDB Deposition Date: 2007/7/30
Updated in MMDB: 2012/11
Experimental Method:
x-ray diffraction
Resolution: 2.8  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 2QSC: trimeric; determined by author and by software (PISA)
Molecular Components in 2QSC
Label Count Molecule
Proteins (3 molecules)
1
FAB F425-b4e8, Light Chain
Molecule annotation
1
FAB F425-b4e8, Heavy Chain
Molecule annotation
1
Envelope Glycoprotein Gp120
Molecule annotation
Chemicals (11 molecules)
1
4
2
4
3
2
4
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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