Structure of the CCR5 Chemokine Receptor–HIV Entry Inhibitor Maraviroc Complex

TLDR

CCR5 is a G protein–coupled receptor that serves as a co‑receptor for HIV‑1 and plays roles in various physiological processes. The authors present a high‑resolution crystal structure of CCR5 bound to Maraviroc, showing that the drug binds a distinct, noncompetitive site and that comparison with CXCR4 illuminates HIV‑1 co‑receptor selectivity. Tan et al.

Abstract

CCR5-Maraviroc Structure The chemokine receptor CCR5, a G protein–coupled receptor best known as a co-receptor during HIV-1 infection, is important in a variety of physiological processes. Tan et al. (p. 1387 , published online 12 September; see the Perspective by Klasse ) now report the high-resolution crystal structure of CCR5 bound to the HIV-1 entry inhibitor, Maraviroc. The structure suggests that Maraviroc acts as a noncompetitive inhibitor by binding to a region of CCR5 that is distinct from the binding site of HIV-1 and chemokines. Comparison of the structure of CCR5 with the other HIV-1 co-receptor, the chemokine receptor CXCR4, provides insight into the co-receptor selectivity of the virus.