Lipid-mediated dimerization of beta2-adrenergic receptor reveals important clues for cannabinoid receptors.
The high-resolution crystal structure of an engineered human beta2-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 beta2-adrenergic receptor as a template. The structural comparison between the two cannabinoid receptor subtypes and the beta2-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.
Dainese
E
E
Department of Biomedical Sciences, University of Teramo, Piazza Aldo Moro 45, Teramo, Italy.
Oddi
S
S
Maccarrone
M
M
D002784:Cholesterol / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D050356:Lipid Metabolism; D017434:Protein Structure, Tertiary; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000378:metabolism*; D043882:Receptors, Cannabinoid / Q000737:chemistry / Q000378:metabolism*
D018343:Receptors, Adrenergic, beta-2; D043882:Receptors, Cannabinoid; D002784:Cholesterol