A proposed molecular model for the carboxy terminus of HIV-1 gp120 showing structural features consistent with the presence of a T-cell alloepitope.
A computer graphics molecular model of the C terminus of gp120 of HIV has been constructed using predicted secondary structure based on homologies with proteins for which X-ray crystallographic data have been published. The model shows sequences known to be important in CD4 binding in close proximity to regions with a high probability of forming alpha helical and beta strand motifs. The orientation adopted by these domains approximates to the known 3D structure of HLA-A2 alpha 2 chain without constraints based on HLA-A2 as a template being introduced. The model may therefore represent an energetically favourable conformation for a part of gp120 which mimics the binding domain for the T-cell receptor on MHC molecules. Recognition of gp120 as an alloepitope in high affinity association with CD4 would explain many of the sequelae of acquired immune deficiency on HIV infection.
Hounsell
E F
EF
Glycoconjugates Section, Clinical Research Centre, Harrow, Middlesex, U.K.
Renouf
D V
DV
Liney
D
D
Dalgleish
A G
AG
Habeshaw
J
J
D000595:Amino Acid Sequence; D015704:CD4 Antigens; D000939:Epitopes / Q000737:chemistry; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology; D015497:HIV-1 / Q000737:chemistry* / Q000276:immunology; D006680:HLA Antigens / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000276:immunology
D015704:CD4 Antigens; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D006680:HLA Antigens