a photon of light and isomerizes to all-trans-retinal, the receptor activating form, causing conformal changes in rhodopsin (bleaching), which activate a phototransduction cascade. Thus, a chemoreceptor is converted to a light or photo(n)receptor. The retinal binding lysine is conserved in almost all opsins, only a few opsins having lost it during evolution. Opsins without the lysine are not light sensitive, including rhodopsin. Rhodopsin is made constitutively (continuously) active by some of those mutations even without light. Also wild-type rhodopsin is constitutively active, if no 11-cis-retinal is bound, but much less. Therefore 11-cis-retinal is an inverse agonist. Such mutations are one cause of autosomal dominant retinitis pigmentosa. Artificially, the retinal binding lysine can be shifted to other positions, even into other transmembrane domains, without changing the activity. The rhodopsin of cattle has 348 amino acids, the retinal binding lysine being Lys296. It was the first opsin whose amino acid sequence and 3D-structure were determined. Its structure has been studied in detail by x-ray crystallography on rhodopsin crystals. Several models (e.g., the bicycle-pedal mechanism, hula-twist mechanism) attempt to explain how the retinal group can change its conformation without clashing with the enveloping rhodopsin protein pocket. Recent data support that rhodopsin is a functional monomer, instead of a dimer, which was the paradigm of G-protein-coupled receptors for many years. Phototransduction Rhodopsin is an essential G-protein coupled receptor in phototransduction. Activation In rhodopsin, the aldehyde group of retinal is covalently linked to the amino group of a lysine residue on the protein in a protonated Schiff base (-NH+=CH-). When rhodopsin absorbs light, its retinal cofactor isomerizes from the 11-cis to the all-trans configuration, and the protein subsequently undergoes a series of relaxations to accommodate the altered shape of the isomerized cofactor. The intermediates formed during this process were first investigated in the laboratory of George Wald, who received the Nobel prize for this research in 1967. The photoisomerization dynamics has been subsequently investigated with time-resolved IR spectroscopy and UV/Vis spectroscopy. A first photoproduct called photorhodopsin forms within 200 femtoseconds after irradiation, followed within picoseconds by a second one called bathorhodopsin with distorted all-trans bonds. This intermediate can be trapped and studied at cryogenic temperatures, and was initially referred to as prelumirhodopsin. In subsequent intermediates lumirhodopsin and metarhodopsin I, the Schiff's base linkage to all-trans retinal remains protonated, and the protein retains its reddish color. The critical change that initiates the neuronal excitation involves the