Spontaneous activation of visual pigments in relation to openness/closedness of chromophore-binding pocket

Abstract

Visual pigments can be spontaneously activated by internal thermal energy, generating noise that interferes with real-light detection. Recently, we developed a physicochemical theory that successfully predicts the rate of spontaneous activity of representative rod and cone pigments from their peak-absorption wavelength (l max ), with pigments having longer l max being noisier. Interestingly, cone pigments may generally be~25 fold noisier than rod pigments of the same l max , possibly ascribed to an 'open' chromophore-binding pocket in cone pigments defined by the capability of chromophore-exchange in darkness. Here, we show in mice that the l max -dependence of pigment noise could be extended even to a mutant pigment, E122Q-rhodopsin. Moreover, although E122Q-rhodopsin shows some cone-pigment-like characteristics, its noise remained quantitatively predictable by the 'non-open' nature of its chromophore-binding pocket as in wildtype rhodopsin. The openness/closedness of the chromophore-binding pocket is potentially a useful indicator of whether a pigment is intended for detecting dim or bright light.

Adaptation of cone pigments found in green rods for scotopic vision through a single amino acid mutation

“…A recent study suggests that the ability to exchange of 11-cisretinal in a pigment with 9-cis-retinal in solution in the dark can be explained by the differences between the structures of the chromophore binding site (open or closed) (29). We assessed the degree of retinal exchange in rhodopsin, zebrafish blue, and Xenopus blue (Fig.…”

Convergent selection pressures drive the evolution of rhodopsin kinetics at high altitudes via nonparallel mechanisms

“…; Yue et al. ). The temperature dependence and physiological importance of these rod equilibria suggests that natural selection may alter rhodopsin stability as a means to modulate visual performance in response to natural temperature variation.…”

Evolution of nonspectral rhodopsin function at high altitudes

“…to organismal visual sensitivity (20,35,36). We tested this experimentally using the prototypical class A GPCR model, bovine (Bos taurus) rhodopsin, because it is well characterized and allows interpretation of the functional results within well-resolved crystal structures (62)(63)(64).…”

“…Recent evidence suggests that visual sensitivity within different habitats is likely maximized through natural variation shifting the spontaneous thermal-and light-activated decay rates of ligand-bound rhodopsin (28,33,34), two distinct kinetic processes of direct relevance to rod photosensitivity (17,20,21). Transgenic animal models have demonstrated that amino acid substitutions destabilizing these inactive and active-forms of rhodopsin can directly affect the dim-light sensitivity of rods (35,36), and are likely responsible for a reduction in rhodopsin-mediated dim-light visual performance in Significance Protein evolution in response to different environments has long been of interest to both evolutionary biologists and biochemists. High-altitude specialist catfishes in the Andes mountains offer an opportunity to examine the molecular adaptations accompanying adaptation to cold environments.…”

“…We hypothesized that rhodopsin in high-altitude Andean specialists has adapted to cold temperatures by increasing kinetic rates, specifically the spontaneous thermal-and light-activated [Metarhodopsin II (MII)] decay rates of rhodopsin, two kinetic processes of direct relevance to organismal visual sensitivity (20,35,36). We sequenced the rhodopsin gene (rh1) from catfish inhabiting a range of altitudes, and combined molecular evolutionary analyses with site-directed mutagenesis experiments to test for cold adaptation in this protein.…”