The Active Site of Melanopsin: The Biological Clock Photoreceptor

摘要

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_(max) = 490 nm) and shows a maximal absorbance (λ_(max) = 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-os-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.