THERAPEUTIC APPROACHES TO HUMAN-IMMUNODEFICIENCY-VIRUS - STRUCTURAL STUDIES ON G-PROTEIN-COUPLED RECEPTORS

Infection by human immunodeficiency virus (HIV) requires the presence of a chemokine receptor on the susceptible cell. The expression of two different chemokine receptors on macrophages and lymphocytes explains the selectivity of different HIV isolates. The rationale behind the c hoice of the chemokine receptor (CCR5) expressed on macrophages as a t herapeutic target is based on the epidemiological studies of the impac t on HIV infectivity of a human mutation that prevents expression of t his receptor. CCR5 is a member of the G-protein-coupled receptor famil y, which has yet to be characterized structurally at atomic resolution . Efforts to model the three-dimensional structure of such receptors a nd to characterize them experimentally are underway in many laboratori es. As an example, structural studies determining the bound conformati on of the C-terminal peptide of the a-subunit of transducin, the relev ant G-protein of vision, with rhodopsin are presented. (C) 1997 Elsevi er Science Inc.