Lipid-mediated dimerization of β₂-adrenergic receptor reveals important clues for cannabinoid receptors

Abstract.

The high-resolution crystal structure of an engineered human β₂-adrenergic receptor has recently been resolved, suggesting a molecular mechanism by which cholesterol may mediate receptor dimerization. Here, we present a critical examination of new structural and functional insights derived from unprecedented preliminary homology modeling of cannabinoid receptors, obtained using the crystal structure of β₂-adrenergic receptor as a template. The structural comparison between the two cannabinoid receptor subtypes and the β₂-adrenergic receptor may be of particular interest, by providing important clues for the elucidation of the structural determinants involved in cholesterol binding. In addition, the implications of G protein coupled receptor dimerization, as well as the role of cholesterol in this process, are briefly discussed.