Crystal structure of rhodopsin: A G protein-coupled receptor

Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled recep tors (GPCRs) respond to a variety of different external stimuli and activat e G proteins. GPCRs share many structural features, including a bundle of s even transmembrane alpha helices connected by six Loops of varying Lengths. We determined the structure of rhodopsin from diffraction data extending t o 2.8 angstroms resolution. The highly organized structure in the extracell ular region, including a conserved disulfide bridge, forms a basis for the arrangement of the seven-helix transmembrane motif. The ground-state chromo phore, Il-cis-retinal, holds the transmembrane region of the protein in the inactive conformation. Interactions of the chromophore with a cluster of k ey residues determine the wavelength of the maximum absorption. Changes in these interactions among rhodopsins facilitate color discrimination. Identi fication of a set of residues that mediate interactions between the transme mbrane helices and the cytoplasmic surface, where C-protein activation occu rs, also suggests a possible structural change upon photoactivation.