The review on rhodopsin, a prototypical G protein-coupled receptor (GPCR) provides an up-to-date picture of its activation mechanism and of its intermediates involved in signal transmission to the G protein.

Our paper is based on the work of Tetsuji Okada, Kris Palczewski and co-workers, who were able to obtain a high-resolution crystal structure of rhodopsin at 2.8 A resolution. As the first and so far only GPCR structure, this structure represents a milestone in GPCR research. Our paper describes how the new insights into structural details allow a reevaluation of biochemical and biophysical studies on rhodopsin going back as far as its discovery in 1878 by Ewald Kühne.

GPCRs transmit extracellular signals into intracellular messages. Extracellular signal molecules include hormones, neurotransmitters, and odorants. The extracellular face of GPCRs binds the signal molecule resulting in a change of the GPCR’s shape. The intracellular face of the GPCRs is then recognized by G proteins, which in turn start complex biochemical processes leading to specific responses inside the cell. Rhodopsin is a prototypical GPCR and is the visual pigment of rod cells in the retina of mammalian eyes. Rhodopsin contains a vitamin A derivative as chromophore which reacts to light signals. Light absorption by the chromophore causes a change of its chemical structure, so that it acts like a signal molecule to GPCRs, eventually initiating an intracellular response leading to vision. GPCRs cover approximately 1% of the human genome, with the rhodopsin-like subfamily being by far the largest. Forty percent of the pharmaceuticals clinically used target GPCRs, which underscores the importance in understanding the mechanisms by which the activity of rhodopsin and GPCRs in general is regulated. Insights into GPCR function will thus improve the design of effective medications and contribute to cure diseases resulting from dysfunction of GPCRs, including eye diseases and cancer.