Perspectives on the counterion switch-induced photoactivation of the G protein-coupled receptor rhodopsin
- Robert R. Birge†,‡ and
- Barry E. Knox‡,§
- †Departments of Chemistry and of Molecular and Cell Biology, University of Connecticut, 55 North Eagleville Road, Storrs, CT 06269; and §Departments of Biochemistry and Molecular Biology and Ophthalmology, State University of New York Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210
Life would not be possible without communication between the cells and the external environment. This critical capability allows cells to monitor the status of the organs and tissues and to respond to environmental threats and opportunities. The process is mediated by a group of membrane-bound proteins known as G protein-coupled receptors (GPCRs). Each GPCR monitors a specific compound or group of compounds and becomes activated when the target ligand (agonist) occupies the active site. The activated GPCR signals the presence of the ligand through interaction with a G protein that migrates within the intracellular medium and directly couples to the activated GPCR. The process provides reliable signaling with variable amplification. There are at least 700 GPCRs encoded in the human genome. Despite significant biological importance, the structure and function of most GPCRs are poorly understood, and a high-resolution crystal structure of only one GPCR, the visual pigment rhodopsin, has been reported (1–3). Visual pigments are seven transmembrane α-helical proteins that bind 11-cis retinal and initiate the light transduction signaling pathway in retinal photoreceptors (4). Although other GPCRs interact with their ligands noncovalently, the visual pigments consist of 11-cis retinal covalently attached to the protein through a conserved lysine residue in the seventh transmembrane helix (HVII, see Fig. 1). After absorption of light, the retinal chromophore isomerizes to the all-trans conformation and triggers a series of conformational changes that lead to the formation of the active state, R* or Meta II (4–9). All-trans retinal is eventually released from the vertebrate protein, and visual pigments can be regenerated from 11-cis retinal spontaneously. Although some consider a photon of light to represent the agonist, a more logical choice is all-trans retinal that is photochemically generated from the 11-cis retinal cofactor. Thus, the visual pigments have …
