Crystal structure of the principal neutralization site of HIV-1.
The crystal structure of a complex between a 24-amino acid peptide from the third variable (V3) loop of human immunodeficiency virus-type 1 (HIV-1) gp 120 and the Fab fragment of a broadly neutralizing antibody (59.1) was determined to 3 angstrom resolution. The tip of the V3 loop containing the Gly-Pro-Gly-Arg-Ala-Phe sequence adopts a double-turn conformation, which may be the basis of its conservation in many HIV-1 isolates. A complete map of the HIV-1 principal neutralizing determinant was constructed by stitching together structures of V3 loop peptides bound to 59.1 and to an isolate-specific (MN) neutralizing antibody (50.1). Structural conservation of the overlapping epitopes suggests that this biologically relevant conformation could be of use in the design of synthetic vaccines and drugs to inhibit HIV-1 entry and virus-related cellular fusion.
Ghiara
J B
JB
Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.
Stura
E A
EA
Stanfield
R L
RL
Profy
A T
AT
Wilson
I A
IA
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000737:chemistry* / Q000276:immunology; D000937:Antigen-Antibody Reactions; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D015483:HIV Antibodies / Q000737:chemistry* / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology; D015497:HIV-1 / Q000737:chemistry* / Q000276:immunology; D006860:Hydrogen Bonding; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry* / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology; D011487:Protein Conformation; D017433:Protein Structure, Secondary
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D007140:Immunoglobulin Fab Fragments; D010446:Peptide Fragments