The Active Site of Melanopsin: The Biological Clock Photoreceptor

The nonvisual ocular photoreceptor melan­opsin, found in the neurons of vertebrate inner retina, absorbs blue light and triggers the “biological clock” of mammals by activating the suprachiasmatic nuclei (a small region of the brain that regulates the circadian rhythms of neuronal and hormonal activities over 24 h cycles). The structure of melan­opsin, however, has yet to be established. Here, we propose for the first time a structural model of the active site of mouse melan­opsin. The homology model is based on the crystal structure of squid rhod­opsin (λ<sub>max</sub> = 490 nm) and shows a maximal absorbance (λ<sub>max</sub> = 447 nm) consistent with the observed absorption of the photo­receptor. The 43 nm spectral shift is due to an increased bond-length alternation of the protonated Schiff base of 11-<i>cis</i>-retinal chromo­phore, induced by N87Q mutation and water-mediated H-bonding interactions with the Schiff base linkage. These findings, analogous to spectral changes observed in the G89Q bovine rhod­opsin mutant, suggest that single site mutations can convert photo­pigments into visual light sensors or nonvisual sensory photo­receptors.