Crystal structure of rhodopsin: a G protein-coupled receptor

Abstract

Heterotrimeric guanine nucleotideÐbinding protein (G protein)Ðcoupled recep-tors (GPCRs) respond to a variety of different external stimuli and activate G proteins. GPCRs share many structural features, including a bundle of seven transmembrane a helices connected by six loops of varying lengths. We de-termined the structure of rhodopsin from diffraction data extending to 2.8 angstroms resolution. The highly organized structure in the extracellular region, including a conserved disulÞde bridge, forms a basis for the arrangement of the seven-helix transmembrane motif. The ground-state chromophore, 11-cis-ret-inal, holds the transmembrane region of the protein in the inactive confor-mation. Interactions of the chromophore with a cluster of key residues deter-mine the wavelength of the maximum absorption. Changes in these interactions among rhodopsins facilitate color discrimination. IdentiÞcation of a set of residues that mediate interactions between the transmembrane helices and the cytoplasmic surface, where G-protein activation occurs, also suggests a possible structural change upon photoactivation