Noncovalent occupancy of the retinal-binding pocket of opsin diminishes bleaching adaptation of retinal cones

Jin, Jing; Crouch, Rosalie K.; Corson, D. Wesley; Katz, Bernice M.; MacNichol, Edward F.; Cornwall, M. Carter

doi:10.1016/0896-6273(93)90155-k

Cited by 98 publications

(62 citation statements)

References 34 publications

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“…5 and Table 2). This is consistent with the finding that ␤-ionone is capable of relieving the desensitization on bleaching of cone cells (30). In contrast, G121L opsin can be significantly activated by ␤-ionone.…”

supporting

confidence: 82%

The C9 methyl group of retinal interacts with glycine-121 in rhodopsin

Han

Groesbeek

Sakmar

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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The visual pigment rhodopsin is a prototypical G protein-coupled receptor. These receptors have seven transmembrane helices and are activated by specific receptor-ligand interactions. Rhodopsin is unusual in that its retinal prosthetic group serves as an antagonist in the dark in the 11-cis conformation but is rapidly converted to an agonist on photochemical cis to trans isomerization. Receptor-ligand interactions in rhodopsin were studied in the light and dark by regenerating site-directed opsin mutants with synthetic retinal analogues. A progressive decrease in light-dependent transducin activity was observed when a mutant opsin with a replacement of Gly 121 was regenerated with 11-cis-retinal analogues bearing progressively larger R groups (methyl, ethyl, propyl) at the C9 position of the polyene chain. A progressive decrease in light activity was also observed as a function of increasing size of the residue at position 121 for both the 11-cis-9-ethyl-and the 11-cis-9-propylretinal pigments. In contrast, a striking increase of receptor activity in the dark-i.e., without chromophore isomerization-was observed when the molecular volume at either position 121 of opsin or C9 of retinal was increased. The ability of bulky replacements at either position to hinder ligand incorporation and to activate rhodopsin in the dark suggests a direct interaction between these two sites. A molecular model of the retinal-binding site of rhodopsin is proposed that illustrates the specific interaction between Gly 121 and the C9 methyl group of 11-cis-retinal. Steric interactions in this region of rhodopsin are consistent with the proposal that movement of transmembrane helices 3 and 6 is concomitant with receptor activation.

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supporting

confidence: 82%

The C9 methyl group of retinal interacts with glycine-121 in rhodopsin

Han

Groesbeek

Sakmar

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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“…According to our model, interaction of the PSB and Glu 113 would result in the deprotonation of surface residues and formation of the inactive state. Interestingly, Jin et al (77) have shown that the addition of ␤-ionone or 9-cis-C17 aldehyde to bleached, intact cones results in partial inactivation of the photoreceptor. ␤-Ionone addition has also been shown to partially reverse the bleach-induced acceleration of guanylyl cyclase activity in cones (78).…”

Section: The Mechanisms Of Opsin Activationmentioning

confidence: 99%

Mechanisms of Opsin Activation

Buczyłko

Saari

Crouch

et al. 1996

Journal of Biological Chemistry

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103

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Rhodopsin is constrained in an inactive conformation by interactions with 11-cis-retinal including formation of a protonated Schiff base with Lys 296. Upon photoisomerization, major structural rearrangements that involve protonation of the active site Glu 113 and cytoplasmic acidic residues, including Glu 134 , lead to the formation of the active form of the receptor, metarhodopsin II b, which decays to opsin. However, an activated receptor may be generated without illumination by addition of all-trans-retinal or its analogues to opsin, as measured in this study by the increased phosphorylation of opsin by rhodopsin kinase. The potency of stimulation depended on the chemical and isomeric nature of the analogues and the length of the polyene chain with all-trans-C17 aldehyde and all-trans-retinal being the most active and trans-C12 aldehyde being the least active. Certain cis-isomers, 11-cis-13-demethyl-retinal and 9-cis-C17 aldehyde, were also active. Most of the retinal analogues tested did not regenerate a spectrally identifiable pigment, and many were incapable of Schiff base formation (ketone, stable oximes, and Schiff basederivatives of retinal). Thus, receptor activation resulted from formation of non-covalent complexes with opsin. pH titrations suggested that an equilibrium exists between partially active (protonated) and inactive (deprotonated) forms of opsin. These findings are consistent with a model in which protonation of one or more cytoplasmic carboxyl groups of opsin is essential for activity. Upon addition of retinoids, the partially active conformation of opsin is converted to a more active intermediate similar to metarhodopsin II b. The model provides an understanding of the structural requirements for opsin activation and an interpretation of the observed activities of natural and experimental opsin mutants.Highly specific protein-protein recognition allows specific signal transduction pathways to be selected from an immense network of inter-and intracellular communications. Structural and chemical complementaries and hydrophobic and electrostatic properties of interacting domains provide precise docking of two or more proteins. Recognition domains may be permanently present in the interacting proteins, assembled because of posttranslational modifications, induced in one or both proteins by a ligand, or formed temporarily as a result of a photochemical reaction. An examination of the principles of proteinprotein recognition is pivotal for understanding the relationship between structure and function of proteins, their participation in physiologically relevant processes, and their regulation.Rhodopsin (Rho), 1 the transducing molecule of vision and a G protein-coupled receptor, undergoes conformational changes upon illumination that ultimately lead to interaction with and activation of the retinal specific G protein (G t ) (reviewed in Ref. 1). The transiently photoactivated Rho is subsequently phosphorylated by rhodopsin kinase (RK) and binds a regulatory protein, arrestin, before it decays to...

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“…Photochemically inactive analogues of retinal-e.g., 11-cis-locked retinal (15)-and fragments of retinal as small as 3-ionone (22) have been shown to neutralize the effects of free opsin. In the course of these experiments, we have examined the role of the 9-methyl group in restoring opsin to its inactive dark-adapted state upon pigment formation.…”

mentioning

confidence: 99%

Relief of opsin desensitization and prolonged excitation of rod photoreceptors by 9-desmethylretinal.

Corson

Cornwall

MacNichol

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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The 9-methyl group of 11-s-retinal plays a crucial role in photoexcitation of the visual pigment rhodopsin. A hydrogen-substituted analogue, 11-cis-9-desmethylretlnal, combines with opsin to form a pigment that produces abnormal photoproducts and diinished activation of the GTP-binding protein transducin in vitro. We have measured the formation of this analogue pigment in bleached salamander rods and determined the size and shape of its quantal response. In addition, we have characterized the influence of opsin and newly formed analogue pigment on the quantal response to native porphyropsin. We find that, as 11-cis-9-desmethylretinal combines with opsin in bleached rods, the amplitude of the quantal response from residual native pigment is elevated by 74.5-fold to 0.15 ± 0.09 pA, a value close to the amplitude of the quantal response before bleach (0.31 ± 0.10 pA). When activated by light, the new analogue pigment produces a quantal response that is ==30-fold smaller and decays ""5 times more slowly than that ofnative pigment in unbleached cells. We conclude that the 9-methyl group of retinal is not critical for conversion of opsin to its nondesensitizing state but that it is critical for the normal processes of activation and deactivation of metarhodopsin that give rise to the quantal response.Photoisomerization of li-cis-retinal (Fig. 1, structure 1) initiates an intramolecular rearrangement of rhodopsin that results in a catalytically active state of rhodopsin, R * (1-5). Deactivation of R* requires phosphorylation by rhodopsin kinase (6, 7) and the subsequent binding of arrestin (3,(7)(8)(9). In isolated photoreceptors, pigment activation and deactivation produce a discrete electrical response with a characteristic amplitude and time course (10,11). In an examination of the steric interactions between the apoprotein opsin and its chromophore, Ganter et al. (12) reported that 11-cis-9-desmethylretinal ( Fig. 1, structure 3) produced abnormal photoproducts and transducin activation that was 8% of the rhodopsin control. Here we examine the influence of the 9-methyl group of retinal on the amplitude and shape of the quantal response in isolated rods.To provide access to the ligand binding pocket ofopsin, the native chromophore (13) 11-cis-3,4-dehydroretinal (Fig. 1, structure 2) was removed by bleaching. Bleaching reduces the sensitivity of a cell by depleting the supply of native pigment and by reducing the amplitude of the quantal response from the residual pigment (14)(15)(16)(17). In the absence of li-cis-retinal, this desensitization persists indefinitely (15,18) and is unresponsive to the addition of all-trans-retinal (15,19) or its removal from opsin by hydroxylamine (20,21). We refer to the persistent component of desensitization that results from response attenuation and does not require the presence of a retinal-containing photoproduct as opsin desensitization. Taken together with the loss of sensitivity resulting from pigment depletion, the total loss of sensitivity is commonly referred to as ...

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Noncovalent occupancy of the retinal-binding pocket of opsin diminishes bleaching adaptation of retinal cones

Cited by 98 publications

References 34 publications

The C9 methyl group of retinal interacts with glycine-121 in rhodopsin

The C9 methyl group of retinal interacts with glycine-121 in rhodopsin

Mechanisms of Opsin Activation

Relief of opsin desensitization and prolonged excitation of rod photoreceptors by 9-desmethylretinal.

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