Activity Switches of Rhodopsin^†

Abstract

Rhodopsin, the visual pigment of the rod photoreceptor cell contains as its light-sensitive cofactor 11-cis retinal, which is bound by a protonated Schiff base between its aldehyde group and the Lys296 side chain of the apoprotein. Light activation is achieved by 11-cis to all-trans isomerization and subsequent thermal relaxation into the active, G protein-binding metarhodopsin II state. Metarhodopsin II decays via two parallel pathways, which both involve hydrolysis of the Schiff base eventually to opsin and released all-trans retinal. Subsequently, rhodopsin's dark state is regenerated by a complicated retinal metabolism, termed the retinoid cycle. Unlike other retinal proteins, such as bacteriorhodopsin, this regeneration cycle cannot be short cut by light, because blue illumination of active metarhodopsin II does not lead back to the ground state but to the formation of largely inactive metarhodopsin III. In this review, mechanistic details of activating and deactivating pathways of rhodopsin, particularly concerning the roles of the retinal, are compared. Based on static and time-resolved UV ⁄ Vis and FTIR spectroscopic data, we discuss a model of the lightinduced deactivation. We describe properties and photoreactions of metarhodopsin III and suggest potential roles of this intermediate for vision.

Not Just Signal Shutoff: The Protective Role of Arrestin-1 in Rod Cells

“…This retinoid cycle constitutes a functional module in which photolyzed ATR is re-isomerized to 11-cis-retinal in order to regenerate rhodopsin (Hofmann et al 2006). In contrast to invertebrate rhodopsin, rhodopsin in vertebrates cannot be regenerated with a second photon absorption (Ritter et al 2008). The complexity of the vertebrate retinoid cycle must confer some benefit by making photoreceptor regeneration ) and arrestin (Arr, 1CF1).…”

Retinal light damage: Mechanisms and protection

“…Grimm et al (2000a) reported that absorption of short wavelength blue light (403nm) by Meta II caused a reversal of rhodopsin bleaching, with regeneration occurring independent of the visual cycle. Ritter et al (2008) concluded that blue light (~400nm) resulted in the conversion of Meta II to Meta III, a 475 nm absorbing intermediate. Whether blue light irradiation reforms native rhodopsin, or whether it leads to Meta III, prolonged blue light should result in the simultaneous presence of all 3 Meta intermediates.…”

Constitutively Active Rhodopsin and Retinal Disease

“…Photon capture by rhodopsin results in the isomerization of 11- cis retinal to all- trans retinal, which triggers a series of structural changes in the receptor (Ye et al, 2010). The result of these changes is a sequence of spectrally distinct intermediate states that eventually culminate in the formation of the active metarhodopsin II ( MII ) state (reviewed in (Ernst et al, 2014; Kandori, Shichida, & Yoshizawa, 2001; Okada, Ernst, Palczewski, & Hofmann, 2001; Ritter, Elgeti, & Bartl, 2008; Shichida & Imai, 1998; Wald, 1968)). Crystal structures for many of the photointermediates of rhodopsin are now available, which provide insights about the sequence of structural changes accompanying rhodopsin activation (Choe et al, 2011; Nakamichi & Okada, 2006a, 2006b; Ruprecht, Mielke, Vogel, Villa, & Schertler, 2004; Salom et al, 2006).…”