Crystal Structure of Rhodopsin: A G Protein-Coupled Receptor

TLDR

G protein‑coupled receptors respond to diverse external stimuli by activating G proteins and share a common architecture of seven transmembrane alpha helices linked by six variable loops. We determined the structure of rhodopsin from diffraction data extending to 2.8 Å resolution. The extracellular region is highly organized with a conserved disulfide bridge that supports the seven‑helix transmembrane motif, the ground‑state chromophore 11‑cis‑retinal locks the protein in an inactive conformation, and its interactions with key residues set the absorption maximum, with variations among rhodopsins enabling color discrimination, while residues linking transmembrane helices to the cytoplasmic surface suggest a structural change upon photoactivation.

Abstract

Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) respond to a variety of different external stimuli and activate G proteins. GPCRs share many structural features, including a bundle of seven transmembrane alpha helices connected by six loops of varying lengths. We determined the structure of rhodopsin from diffraction data extending to 2.8 angstroms resolution. The highly organized structure in the extracellular region, including a conserved disulfide bridge, forms a basis for the arrangement of the seven-helix transmembrane motif. The ground-state chromophore, 11-cis-retinal, holds the transmembrane region of the protein in the inactive conformation. Interactions of the chromophore with a cluster of key residues determine the wavelength of the maximum absorption. Changes in these interactions among rhodopsins facilitate color discrimination. Identification 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.