Rhodopsin and retinitis pigmentosa: shedding light on structure and function

Rhodopsin is the dim-light activated photoreceptor located in the rod cells of the eye. It belongs to the large superfamily of G-protein-coupled receptors (GPCRs). Many consider it the proto-typical GPCR as numerous studies since its cloning in 1983 (Nathans and Hogness 1983) have established many fundamental principles of seven transmembrane-spanning GPCRs. Abundant expression in the rod's outer segment, constituting about 90% of the total membrane protein in the discs, and the development of techniques to purify large quantities of functional protein has facilitated this process. Another distinct feature is rhodopsin's ligand, 11-cis-retinal, which is covalently bound via a Schiff base to transmembrane seven (TM VII), allowing extensive spectroscopic studies. Exciting recent developments include the discovery of naturally occurring mutations that lead to retinal degeneration, the determination of transmembrane movements using electron paramagnetic resonance (EPR) and biochemical techniques, and the discovery of its 3D X-ray crystal structure, the first among GPCRs. The impact of these major advances will be discussed in this review.