Opsins visual pigments

The visual pigment present in rods has been termed rhodopsin and consists of 11-m-retinal, a derivative of vitamin A1( and a lipoprotein called opsin. Recent evidence(43) suggests that in native rhodopsin the retinal chromo-phore is covalently bonded to a phosphatidylethanolamine residue of the lipid portion of opsin. The structure of 1 l-cis-retinal is as follows ... 

Rhodopsin is a seven ot-helix trans-membrane protein and visual pigment of the vertebrate rod photoreceptor cells that mediate dim light vision. In this photoreceptor, retinal is the chromophore bound by opsin protein, covalently linked to Lys296 by a Schiff base linkage. Kpega et al.64 have studied NMR spectra of Schiff bases being derivatives of all-frans retinal and amino-p-cyclodextrins as a model of rhodopsin, where p-cyclodextrin plays a role of a binding pocket. On the basis of analysis of the chemical shift differences for the model compound in the presence and in the absence of adamantane carboxylate, it has been shown that the derivative of 3-amino-p-cyclodextrin forms dimer in water and retinoid is inserted into p-cyclodextrin cavity [31]. 

A deficiency of vitamin A leads to vision defects, including a visual impairment at low light levels, termed night blindness. For the processes of vision, retinol needs to be converted first by oxidation into the aldehyde retinal, and then by enzymic isomerization to cw-retinal. c -Retinal is then bound to the protein opsin in the retina via an imine linkage (see Section 7.7.1) to give the red visual pigment rhodopsin. 

Soni BG, Foster RG 1997 A novel and ancient vertebrate opsin. FEBS Lett 406 279—283 Soni BG, Philp AR, Knox BE, Foster RG 1998 Novel retinal photoreceptors. Nature 394 27—28 Starace DM, Knox BE 1997 Activation of transducin by a Xenopus short wavelength visual pigment. J Biol Chem 272 1095—1100... 

By introducing fluorine atoms to the polyenic system of retinal, the geometry, electronic properties, hydrophobicity, and absorption properties of the molecule will be modified. Thus, fluoro derivatives of retinal are useful tools to understand the interactions between retinal and opsin, especially on the level of charge and hydrophobic effects at the protein site. Moreover, fluorine atoms are probes in NMR and allow studies on model molecules of visual pigments Consequently, syntheses of mono-, di-, and trifluoro derivatives of retinal have been the subject of many investigations. 

Photochemical cis-trans isomerization in a conjugated polyene system is thought to be the crucial primary process in vision. The visual pigment (rhodopsin) is derived from 11 -crs-retinal by reaction of the aldehyde group with an amino substituent in a protein (opsin). There is considerable distortion in the geometry of this chromophoric group anyway, because of the spatial requirements of the protein... 

Saari has made the bold statement that Three derivatives of 11-cis-retinaldehyde serve as the chromophores of all known visual pigments. They are complexed with a protein component (an opsin), and the resulting protein-retinoid interactions determine the spectral sensitivity of the visual pigment. 85 No reference is given for this statement nor is any explanation of how these complexes exhibit an absorption spectrum in the visual region. However, except for the substitution of all-trans for 11 -cis in the above quotation and a slight modification to the retinoid involved, this work agrees completely with the statement and provides an explanation for how it is applied. 

The opsin consists of protein (ca. 80-85% of which is rhodopsin), phospholipids and carbohydrates and contains very little cholesterol (1-3%) (for a review, see [6]). While the molecular weight (e.g., 40000 for bovine rhodopsin) [7], carbohydrate [8,9], lipid and amino acid [10-12] composition have been established for some rhodopsins, there is as yet no example of a visual pigment for which the full amino acid sequence is known. Only a quarter of about the 300 residues of rhodopsin have been sequenced [13,14], 39 residues at the N-terminus and 40 residues at the C-terminus. The structure of the moiety containing retinal, i.e., retinal-lysine-alanine, which is located in the carboxy-terminal region has, however, been elucidated ([15] see also [78] and references therein). The N-terminal residue was identified as acetylmethionine [16]. 

The study of visual pigment analogs serves to clarify the nature of chromophore-opsin interactions in visual pigments. Visual pigment analogs are modified retinals bound to opsins, which can be investigated by spectroscopic and biochemical methods. 

A. Kropf, unpublished work), all combined with cattle opsin to give visual pigment analogs. 

Recently, even highly modified retinals, in which the trimethylcyclohexenyl ring was replaced with an aromatic ring, did form visual pigment analogs with cattle opsin [183,191], The pigment analogs from retinals 41, 42, 43 and 44, however, were... 

A large number of both theoretical and experimental models were put forward to account for the opsin shifts encountered in visual pigments ... 

Akhtar et al. [74] proposed that, in rhodopsin, an acceptor group on the protein forms a charge-transfer complex with the unprotonated Schiff base of retinal furthermore, upon ll-cis to trans isomerization, separation of donor and acceptor moieties would occur and the Schiff base linkage would be exposed to hydrolysis. This model can now be discarded as unrealistic the resonance Raman experiments have shown that it is not an unprotonated Schiff base, but a protonated base which is bound to opsin. Further, this and related models were examined by Komatsu and Suzuki [223] using theoretical calculations, who found that charge-transfer type models cannot satisfactorily explain the red shifts seen in visual pigments. 

A series of hydroretinals were synthesized and were bound to bovine opsin to form visual pigment analogs, the hydrorhodopsins [92]. Model protonated Schiff bases were also prepared from each of these retinals, and the magnitudes of the opsin shifts were determined. Table 1 summarizes the data obtained and shows the opsin shift for bovine rhodopsin for comparative purposes. Binding studies were also carried out to ascertain that the hydroretinals occupy the same binding site as 11-cK-retinal in rhodopsin. This is required to show the relevance of the data to the natural system. 

Visual excitation (1) in both vertebrates and invertebrates is initiated via light absorption by visual pigments consisting of a chromophore covalently bound to an apo-protein, opsin. Biochemical extraction studies have shown that in all pigments the chromophore is a Schiff base derivative of 11-cis retinal (Fig. 

Thu molecular mechanism of action of vitamin A in the visual process has been under investigation for many years. Wald in 1(168 and Morton in 1972" characterized this mechanism of action. The chemistry of vision was reviewed comprehensively in Accotmi.t of Clwmical Research (1975) by numerous investigators. These reviews include theoretical studies of the visual chromophorc. characleri/alion of ihfldopsin in synthetic systems, dynamic processes in vertebrate rod visual pigments and their membranes, and the dynamics of the visual protein opsin. ""... 

---