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

Wendy Wing Sze Yue,Takahiro Yamashita,King-Wai Yau,Dong-Gen Luo,Rikard Frederiksen,Xiaozhi Ren,Yoshinori Shichida,M Carter Cornwall

doi:10.7554/elife.18492

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 (λmax), with pigments having longer λmax being noisier. Interestingly, cone pigments may generally be ~25 fold noisier than rod pigments of the same λmax, 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 λmax-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 wild-type 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.

Highlights

Retinal rod and cone photoreceptors, having similar phototransduction mechanisms, elaborate different morphological and molecular features for functioning in dim and bright light, respectively
Rod pigments have a low rate of spontaneous activation in darkness (Baylor et al, 1980), offering a good signal-to-noise ratio for dim-light vision
Spontaneous activation originates from internal thermal energy of the pigment molecule, generating an electrical event indistinguishable from that triggered by an absorbed photon (Baylor et al, 1980), interfering with real-light detection

Summary

Introduction

Retinal rod and cone photoreceptors, having similar phototransduction mechanisms, elaborate different morphological and molecular features for functioning in dim and bright light, respectively. By using multi-vibrational-mode statistical mechanics (Ala-Laurila et al, 2004; Hinshelwood, 1940; St George, 1952), the theory was able to explain quantitatively the lmaxdependence of pigment noise, with the noise increasing by 107-fold from blue (short-wavelengthsensitive, or SWS) cone pigment to red (long-wavelength-sensitive, or LWS) cone pigment (Fu et al, 2008; Kefalov et al, 2003; Luo et al, 2011) This theory clarifies the decades-long uncertainty about whether the spontaneous pigment activity arises from canonical isomerization of the pigment’s chromophore (as in photoisomerization) or from some different, unknown chemical reaction. We can check in this ‘hybrid’ pigment the correlation between pigment noise and openness/closedness of the chromophore-binding pocket as we hypothesized

Results and discussion

Materials and methods

Funding Funder National Eye Institute