A Phe-rich region in short-wavelength sensitive opsins is responsible for their aggregation in the absence of 11-cis-retinal.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhang T
PROVIDER: S-EPMC3758227 | biostudies-literature | 2013 Aug
REPOSITORIES: biostudies-literature
Publications
A Phe-rich region in short-wavelength sensitive opsins is responsible for their aggregation in the absence of 11-cis-retinal.
FEBS letters 20130620 15
Human blue and mouse S-opsin are prone to aggregation in the absence of 11-cis-retinal, which underlie the rapid cone degeneration in human patients and animal models of Leber congenital amaurosis (LCA). By in silico analysis and domain swapping experiments, we show that a Phe-rich region in short-wavelength sensitive (SWS) opsins, but not in medium/long-wavelength sensitive opsins, is responsible for SWS opsin aggregation. Mutagenesis studies suggest that Phe residues in this region are critica ...[more]
Similar Datasets
Project description:One of the basic and unresolved puzzles in the chemistry of vision concerns the natural selection of 11-cis-retinal as the light-sensing chromophore in visual pigments. A detailed computational examination of the structure, stability, energetics, and spectroscopy of 7-cis-, 9-cis-, 11-cis-, and 13-cis-retinal isomers in vertebrate (bovine, monkey) and invertebrate (squid) visual pigments was carried out using a hybrid quantum mechanics/molecular mechanics (QM/MM) method. The results show that the electrostatic interaction between retinal and opsin dominates the natural selection of 11-cis-retinal over other cis isomers in the dark state. In all of the pigments, 9-cis-retinal was found to be only slightly higher in energy than 11-cis-retinal, which provides strong evidence for the presence of 9-cis-rhodopsin in nature. 7-cis-Retinal is suggested to be an "upside-down" version of the all-trans isomer because the structural rearrangements observed for 7-cis-rhodopsin from squid were found to be very similar to those for squid bathorhodopsin. The progressive red shift in the calculated absorption wavelength (?(max)) (431, 456, 490, and 508 nm for the 7-cis-, 9-cis-, 11-cis-, and 13-cis-retinal isomers) is due to the decrease in bond length alternation of the retinal.
| S-EPMC3223315 | biostudies-literature
Project description:Photoisomerization of the 11-cis-retinal chromophore of rod and cone visual pigments to an all-trans-configuration is the initiating event for vision in vertebrates. The regeneration of 11-cis-retinal, necessary for sustained visual function, is an endergonic process normally conducted by specialized enzyme systems. However, 11-cis-retinal also can be formed through reverse photoisomerization from all-trans-retinal. A nonvisual opsin known as retinal pigment epithelium (RPE)-retinal G-protein-coupled receptor (RGR) was previously shown to mediate visual chromophore regeneration in photic conditions, but conflicting results have cast doubt on its role as a photoisomerase. Here, we describe high-level production of 11-cis-retinal from RPE membranes stimulated by illumination at a narrow band of wavelengths. This activity was associated with RGR and enhanced by cellular retinaldehyde-binding protein (CRALBP), which binds the 11-cis-retinal produced by RGR and prevents its re-isomerization to all-trans-retinal. The activity was recapitulated with cells heterologously expressing RGR and with purified recombinant RGR. Using an RGR variant, K255A, we confirmed that a Schiff base linkage at Lys-255 is critical for substrate binding and isomerization. Single-cell RNA-Seq analysis of the retina and RPE tissue confirmed that RGR is expressed in human and bovine RPE and Müller glia, whereas mouse RGR is expressed in RPE but not in Müller glia. These results provide key insights into the mechanisms of physiological retinoid photoisomerization and suggest a novel mechanism by which RGR, in concert with CRALBP, regenerates the visual chromophore in the RPE under sustained light conditions.
| S-EPMC6916499 | biostudies-literature
Project description:BackgroundThe behavioral photosensitivity of animals could be quantified via the optomotor response (OMR), for example, and the luminous efficiency function (the range of visible light) should largely rely on the repertoire and expression of light-absorbing proteins in the retina, i.e., the opsins. In fact, the OMR under red light was suppressed in medaka lacking the red (long-wavelength sensitive [LWS]) opsin.ResultsWe investigated the ultraviolet (UV)- or blue-light sensitivity of medaka lacking the violet (short-wavelength sensitive 1 [SWS1]) and blue (SWS2) opsins. The sws1/sws2 double or sws1/sws2/lws triple mutants were as viable as the wild type. The remaining green (rhodopsin 2 [RH2]) or red opsins were not upregulated. Interestingly, the OMR of the double or triple mutants was equivalent or even increased under UV or blue light (λ = 350, 365, or 450 nm), which demonstrated that the rotating stripes (i.e., changes in luminance) could fully be recognized under UV light using RH2 alone. The OMR test using dichromatic stripes projected onto an RGB display consistently showed that the presence or absence of SWS1 and SWS2 did not affect the equiluminant conditions.ConclusionsRH2 and LWS, but not SWS1 and SWS2, should predominantly contribute to the postreceptoral processes leading to the OMR or, possibly, to luminance detection in general, as the medium-wavelength-sensitive and LWS cones, but not the SWS cones, are responsible for luminance detection in humans.
| S-EPMC10722765 | biostudies-literature
Project description:The vertebrate visual photoreceptor rhodopsin (Rho) is a unique G protein-coupled receptor as it utilizes a covalently tethered inverse agonist (11-cis-retinal) as the native ligand. Previously, electrophysiological studies showed that ligand binding of 11-cis-retinal in dark-adapted Rho was essentially irreversible with a half-life estimated to be 420 years, until after thermal isomerization to all-trans-retinal, which then slowly dissociates. This long lifetime of 11-cis-retinal binding was considered to be physiologically important for minimizing background signal (dark noise) of the visual system. However, in vitro biochemical studies on the thermal stability of Rho showed that Rho decays with a half-life on the order of days. In this study, we resolve the discrepancy by measuring the chromophore exchange rate of the bound 11-cis-retinal chromophore with free 9-cis-retinal from Rho in an in vitro phospholipid/detergent bicelle system. We conclude that the thermal decay of Rho primarily proceeds through spontaneous breaking of the covalent linkage between opsin and 11-cis-retinal, which was overlooked in the electrophysiological recording. We estimate that this slow spontaneous release of 11-cis-retinal from Rho should result in 104 to 105 free opsin molecules in a dark-adapted rod cell-a number that is three orders of magnitude higher than previously expected. We also discuss the physiological implications of these findings on the basal activity of opsins and the associated dark noise in the visual system.
| S-EPMC5232893 | biostudies-literature
Project description:Cone photoreceptors require effective pigment regeneration mechanisms to maintain their sensitivity in the light. Our previous studies in carp cones suggested the presence of an unconventional and very effective mechanism to produce 11-cis retinal, the necessary component in pigment regeneration. In this reaction (aldehyde-alcohol redox coupling reaction, AL-OL coupling reaction), formation of 11-cis retinal, i.e. oxidation of 11-cis retinol is coupled to reduction of an aldehyde at a 1:1 molar ratio without exogenous NADP(H) which is usually required in this kind of reaction. Here, we identified carp retinol dehydrogenase 13-like (RDH13L) as an enzyme catalyzing the AL-OL coupling reaction. RDH13L was partially purified from purified carp cones, identified as a candidate protein, and its AL-OL coupling activity was confirmed using recombinant RDH13L. We further examined the substrate specificity, subcellular localization, and expression level of RDH13L. Based on these results, we concluded that RDH13L contributes to a significant part, but not all, of the AL-OL coupling activity in carp cones. RDH13L contained tightly bound NADP(+) which presumably functions as a cofactor in the reaction. Mouse RDH14, a mouse homolog of carp RDH13L, also showed the AL-OL coupling activity. Interestingly, although carp cone membranes, carp RDH13L and mouse RDH14 all showed the coupling activity at 15-37 °C, they also showed a conventional NADP(+)-dependent 11-cis retinol oxidation activity above 25 °C without addition of aldehydes. This dual mechanism of 11-cis retinal synthesis attained by carp RDH13L and mouse RDH14 probably contribute to effective pigment regeneration in cones that function in the light.
| S-EPMC4317047 | biostudies-literature
Project description:Color discrimination in the vertebrate retina is mediated by a combination of spectrally distinct cone photoreceptors, each expressing one of multiple cone opsins. The opsin genes diverged early in vertebrate evolution into four classes maximally sensitive to varying wavelengths of light: UV (SWS1), blue (SWS2), green (RH2), and red (LWS) opsins. Although the tetrachromatic cone system is retained in most nonmammalian vertebrate lineages, the transcriptional mechanism underlying gene expression of the cone opsins remains elusive, particularly for SWS2 and RH2 opsins, both of which have been lost in the mammalian lineage. In zebrafish, which have all four cone subtypes, rh2 opsin gene expression depends on a homeobox transcription factor, sine oculis homeobox 7 (Six7). However, the six7 gene is found only in the ray-finned fish lineage, suggesting the existence of another evolutionarily conserved transcriptional factor(s) controlling rh2 opsin expression in vertebrates. Here, we found that the reduced rh2 expression caused by six7 deficiency was rescued by forced expression of six6b, which is a six7-related transcription factor conserved widely among vertebrates. The compensatory role of six6b was reinforced by ChIP-sequencing analysis, which revealed a similar pattern of Six6b- and Six7-binding sites within and near the cone opsin genes. TAL effector nuclease-induced genetic ablation of six6b and six7 revealed that they coordinately regulate SWS2 opsin gene expression. Mutant larvae deficient for these transcription factors showed severely impaired visually driven foraging behavior. These results demonstrate that in zebrafish, six6b and six7 govern expression of the SWS2 and RH2 opsins responsible for middle-wavelength sensitivity, which would be physiologically important for daylight vision.
| S-EPMC6410792 | biostudies-literature
Project description:Opsins allow us to see. They are G-protein-coupled receptors and bind as ligand retinal, which is bound covalently to a lysine in the seventh transmembrane domain. This makes opsins light-sensitive. The lysine is so conserved that it is used to define a sequence as an opsin and thus phylogenetic opsin reconstructions discard any sequence without it. However, recently, opsins were found that function not only as photoreceptors but also as chemoreceptors. For chemoreception, the lysine is not needed. Therefore, we wondered: Do opsins exists that have lost this lysine during evolution? To find such opsins, we built an automatic pipeline for reconstructing a large-scale opsin phylogeny. The pipeline compiles and aligns sequences from public sources, reconstructs the phylogeny, prunes rogue sequences, and visualizes the resulting tree. Our final opsin phylogeny is the largest to date with 4956 opsins. Among them is a clade of 33 opsins that have the lysine replaced by glutamic acid. Thus, we call them gluopsins. The gluopsins are mainly dragonfly and butterfly opsins, closely related to the RGR-opsins and the retinochromes. Like those, they have a derived NPxxY motif. However, what their particular function is, remains to be seen.
| S-EPMC9368030 | biostudies-literature
Project description:BackgroundColor vision and phototactic behavior based on opsins are important for the fitness of insects because of their roles in foraging and mate choice. Related topics, including the duplication and loss of opsin genes, have been well investigated in insect orders such as Coleoptera, Lepidoptera, Hymenoptera, Odonata and Orthoptera, and the findings have been used to develop pest management strategies involving light trapping. Mirid bugs of Hemiptera, which are pests that cause heavy economic losses, show capacity for color discrimination and phototaxis. However, the opsins in mirid bugs remain uncharacterized. Herein, we examined five species to investigate the evolution of opsins in the family Miridae.ResultsUsing RNA-seq, we identified several contigs showing high identity with opsins, including four contigs in Apolygus lucorum and three contigs each in Adelphocoris suturalis, Adelphocoris fasciaticollis, Adelphocoris lineolatus and Nesidiocoris tenuis. Phylogenetic analyses indicated that one of these genes clustered with ultraviolet-sensitive (UV) opsins and that the others clustered with long-wavelength (LW) opsins, suggesting that duplication of LW opsins and loss of blue light-sensitive (B) opsins occurred in mirid bugs. The existence of introns in the LW opsins of mirid bugs suggested that the duplication events were DNA based. Both LW1 and LW2 opsins of mirid bugs were found to be under strong purifying selection. The LW1 opsins were significantly more highly expressed than the LW2 and UV opsins.ConclusionsWe identified the opsins of mirid bugs using five selected mirid species as a representative sample. Phylogenetic analyses clustered one of the genes with UV opsins and the others with LW opsins, suggesting the occurrence of LW opsin duplication and B opsin loss during the evolution of mirid bugs. Intron detection suggested that the identified duplication event was DNA based. The evidence of strong purifying selection and the relatively high expression levels suggested that these opsins exhibit fundamental functions in mirid bugs.
| S-EPMC8074501 | biostudies-literature
Project description:The evolution of a variety of important chromophore-dependent biological processes, including microbial light sensing and mammalian color vision, relies on protein modifications that alter the spectral characteristics of a bound chromophore. Three different color opsins share the same chromophore, but have three distinct absorptions that together cover the entire visible spectrum, giving rise to trichromatic vision. The influence of opsins on the absorbance of the chromophore has been studied through methods such as model compounds, opsin mutagenesis, and computational modeling. The recent development of rhodopsin mimic that uses small soluble proteins to recapitulate the binding and wavelength tuning of the native opsins provides a new platform for studying protein-regulated spectral tuning. The ability to achieve far-red shifted absorption in the rhodopsin mimic system was attributed to a combination of the lack of a counteranion proximal to the iminium, and a uniformly neutral electrostatic environment surrounding the chromophore.
| S-EPMC4104663 | biostudies-literature
Project description:Cetaceans have a long history of commitment to a fully aquatic lifestyle that extends back to the Eocene. Extant species have evolved a spectacular array of adaptations in conjunction with their deployment into a diverse array of aquatic habitats. Sensory systems are among those that have experienced radical transformations in the evolutionary history of this clade. In the case of vision, previous studies have demonstrated important changes in the genes encoding rod opsin (RH1), short-wavelength sensitive opsin 1 (SWS1), and long-wavelength sensitive opsin (LWS) in selected cetaceans, but have not examined the full complement of opsin genes across the complete range of cetacean families. Here, we report protein-coding sequences for RH1 and both color opsin genes (SWS1, LWS) from representatives of all extant cetacean families. We examine competing hypotheses pertaining to the timing of blue shifts in RH1 relative to SWS1 inactivation in the early history of Cetacea, and we test the hypothesis that some cetaceans are rod monochomats. Molecular evolutionary analyses contradict the "coastal" hypothesis, wherein SWS1 was pseudogenized in the common ancestor of Cetacea, and instead suggest that RH1 was blue-shifted in the common ancestor of Cetacea before SWS1 was independently knocked out in baleen whales (Mysticeti) and in toothed whales (Odontoceti). Further, molecular evidence implies that LWS was inactivated convergently on at least five occasions in Cetacea: (1) Balaenidae (bowhead and right whales), (2) Balaenopteroidea (rorquals plus gray whale), (3) Mesoplodon bidens (Sowerby's beaked whale), (4) Physeter macrocephalus (giant sperm whale), and (5) Kogia breviceps (pygmy sperm whale). All of these cetaceans are known to dive to depths of at least 100 m where the underwater light field is dim and dominated by blue light. The knockout of both SWS1 and LWS in multiple cetacean lineages renders these taxa rod monochromats, a condition previously unknown among mammalian species.
| S-EPMC3630094 | biostudies-literature