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Progress in Retinal and Eye Research Mar 2023The light sensor of vertebrate scotopic (low-light) vision, rhodopsin, is a G-protein-coupled receptor comprising a polypeptide chain with bound chromophore,... (Review)
Review
The light sensor of vertebrate scotopic (low-light) vision, rhodopsin, is a G-protein-coupled receptor comprising a polypeptide chain with bound chromophore, 11-cis-retinal, that exhibits remarkable physicochemical properties. This photopigment is extremely stable in the dark, yet its chromophore isomerises upon photon absorption with 70% efficiency, enabling the activation of its G-protein, transducin, with high efficiency. Rhodopsin's photochemical and biochemical activities occur over very different time-scales: the energy of retinaldehyde's excited state is stored in <1 ps in retinal-protein interactions, but it takes milliseconds for the catalytically active state to form, and many tens of minutes for the resting state to be restored. In this review, we describe the properties of rhodopsin and its role in rod phototransduction. We first introduce rhodopsin's gross structural features, its evolution, and the basic mechanisms of its activation. We then discuss light absorption and spectral sensitivity, photoreceptor electrical responses that result from the activity of individual rhodopsin molecules, and recovery of rhodopsin and the visual system from intense bleaching exposures. We then provide a detailed examination of rhodopsin's molecular structure and function, first in its dark state, and then in the active Meta states that govern its interactions with transducin, rhodopsin kinase and arrestin. While it is clear that rhodopsin's molecular properties are exquisitely honed for phototransduction, from starlight to dawn/dusk intensity levels, our understanding of how its molecular interactions determine the properties of scotopic vision remains incomplete. We describe potential future directions of research, and outline several major problems that remain to be solved.
Topics: Photoreceptor Cells; Retina; Rhodopsin; Transducin; Vision, Ocular; Animals
PubMed: 36273969
DOI: 10.1016/j.preteyeres.2022.101116 -
Proceedings of the National Academy of... Nov 2003Microbial-type rhodopsins are found in archaea, prokaryotes, and eukaryotes. Some of them represent membrane ion transport proteins such as bacteriorhodopsin, a...
Microbial-type rhodopsins are found in archaea, prokaryotes, and eukaryotes. Some of them represent membrane ion transport proteins such as bacteriorhodopsin, a light-driven proton pump, or channelrhodopsin-1 (ChR1), a recently identified light-gated proton channel from the green alga Chlamydomonas reinhardtii. ChR1 and ChR2, a related microbial-type rhodopsin from C. reinhardtii, were shown to be involved in generation of photocurrents of this green alga. We demonstrate by functional expression, both in oocytes of Xenopus laevis and mammalian cells, that ChR2 is a directly light-switched cation-selective ion channel. This channel opens rapidly after absorption of a photon to generate a large permeability for monovalent and divalent cations. ChR2 desensitizes in continuous light to a smaller steady-state conductance. Recovery from desensitization is accelerated by extracellular H+ and negative membrane potential, whereas closing of the ChR2 ion channel is decelerated by intracellular H+. ChR2 is expressed mainly in C. reinhardtii under low-light conditions, suggesting involvement in photoreception in dark-adapted cells. The predicted seven-transmembrane alpha helices of ChR2 are characteristic for G protein-coupled receptors but reflect a different motif for a cation-selective ion channel. Finally, we demonstrate that ChR2 may be used to depolarize small or large cells, simply by illumination.
Topics: Algal Proteins; Animals; Cations; Cell Line; Chlamydomonas reinhardtii; Cricetinae; Female; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Ion Channel Gating; Ion Channels; Light; Membrane Potentials; Oocytes; Photobiology; Protozoan Proteins; Recombinant Proteins; Rhodopsin; Xenopus laevis
PubMed: 14615590
DOI: 10.1073/pnas.1936192100 -
Biochimica Et Biophysica Acta May 2014Proteorhodopsins are the most abundant retinal based photoreceptors and their phototrophic function might be relevant in marine ecosystems. Here, we describe their... (Review)
Review
Proteorhodopsins are the most abundant retinal based photoreceptors and their phototrophic function might be relevant in marine ecosystems. Here, we describe their remarkable molecular properties with a special focus on the green absorbing variant. Its distinct features include a high pKa value of the primary proton acceptor stabilized through an interaction with a conserved histidine, a long-range interaction between the cytoplasmic EF loop and the chromophore entailing a particular mode of color tuning and a variable proton pumping vectoriality with complex voltage-dependence. The proteorhodopsin family represents a profound example for structure-function relationships. Especially the development of a biophysical understanding of green proteorhodopsin is an excellent example for the unique opportunities offered by a combined approach of advanced spectroscopic and electrophysiological methods. This article is part of a Special Issue entitled: Retinal Proteins-You can teach an old dog new tricks.
Topics: Amino Acid Sequence; Animals; Histidine; Hydrogen-Ion Concentration; Ion Transport; Light; Models, Molecular; Molecular Sequence Data; Patch-Clamp Techniques; Protein Conformation; Proteobacteria; Protons; Retinaldehyde; Rhodopsin; Rhodopsins, Microbial; Structure-Activity Relationship; Xenopus
PubMed: 24060527
DOI: 10.1016/j.bbabio.2013.09.010 -
Acta Pharmacologica Sinica Mar 2012Rhodopsin is the first G-protein-coupled receptor (GPCR) with its three-dimensional structure solved by X-ray crystallography. The crystal structure of rhodopsin has... (Review)
Review
Rhodopsin is the first G-protein-coupled receptor (GPCR) with its three-dimensional structure solved by X-ray crystallography. The crystal structure of rhodopsin has revealed the molecular mechanism of photoreception and signal transduction in the visual system. Although several other GPCR crystal structures have been reported over the past few years, the rhodopsin structure remains an important model for understanding the structural and functional characteristics of other GPCRs. This review summarizes the structural features, the photoactivation, and the G protein signal transduction of rhodopsin.
Topics: Animals; Crystallography, X-Ray; Humans; Models, Molecular; Protein Conformation; Receptors, G-Protein-Coupled; Rhodopsin; Signal Transduction; Structure-Activity Relationship
PubMed: 22266727
DOI: 10.1038/aps.2011.171 -
Advances in Pharmacology (San Diego,... 2014Rhodopsin is the light receptor in rod photoreceptor cells of the retina that initiates scotopic vision. In the dark, rhodopsin is bound to the chromophore 11-cis... (Review)
Review
Rhodopsin is the light receptor in rod photoreceptor cells of the retina that initiates scotopic vision. In the dark, rhodopsin is bound to the chromophore 11-cis retinal, which locks the receptor in an inactive state. The maintenance of an inactive rhodopsin in the dark is critical for rod photoreceptor cells to remain highly sensitive. Perturbations by mutation or the absence of 11-cis retinal can cause rhodopsin to become constitutively active, which leads to the desensitization of photoreceptor cells and, in some instances, retinal degeneration. Constitutive activity can arise in rhodopsin by various mechanisms and can cause a variety of inherited retinal diseases including Leber congenital amaurosis, congenital night blindness, and retinitis pigmentosa. In this review, the molecular and structural properties of different constitutively active forms of rhodopsin are overviewed, and the possibility that constitutive activity can arise from different active-state conformations is discussed.
Topics: Animals; Humans; Mutation; Phenotype; Retinal Diseases; Rhodopsin
PubMed: 24931191
DOI: 10.1016/B978-0-12-417197-8.00001-8 -
Vision Research Dec 2006
Topics: Animals; Humans; Retinal Rod Photoreceptor Cells; Rhodopsin; Transducin
PubMed: 17098052
DOI: 10.1016/j.visres.2006.10.009 -
Biochemistry. Biokhimiia Oct 2023The diversity of the retinal-containing proteins (rhodopsins) in nature is extremely large. Fundamental similarity of the structure and photochemical properties unites... (Review)
Review
The diversity of the retinal-containing proteins (rhodopsins) in nature is extremely large. Fundamental similarity of the structure and photochemical properties unites them into one family. However, there is still a debate about the origin of retinal-containing proteins: divergent or convergent evolution? In this review, based on the results of our own and literature data, a comparative analysis of the similarities and differences in the photoconversion of the rhodopsin of types I and II is carried out. The results of experimental studies of the forward and reverse photoreactions of the bacteriorhodopsin (type I) and visual rhodopsin (type II) rhodopsins in the femto- and picosecond time scale, photo-reversible reaction of the octopus rhodopsin (type II), photovoltaic reactions, as well as quantum chemical calculations of the forward photoreactions of bacteriorhodopsin and visual rhodopsin are presented. The issue of probable convergent evolution of type I and type II rhodopsins is discussed.
Topics: Rhodopsin; Bacteriorhodopsins; Photochemistry
PubMed: 38105022
DOI: 10.1134/S0006297923100097 -
Cellular and Molecular Life Sciences :... Aug 2022Opsins are universal photoreceptive proteins in animals. Vertebrate rhodopsin in ciliary photoreceptor cells photo-converts to a metastable active state to regulate...
Opsins are universal photoreceptive proteins in animals. Vertebrate rhodopsin in ciliary photoreceptor cells photo-converts to a metastable active state to regulate cyclic nucleotide signaling. This active state cannot photo-convert back to the dark state, and thus vertebrate rhodopsin is categorized as a mono-stable opsin. By contrast, mollusk and arthropod rhodopsins in rhabdomeric photoreceptor cells photo-convert to a stable active state to stimulate IP/calcium signaling. This active state can photo-convert back to the dark state, and thus these rhodopsins are categorized as bistable opsins. Moreover, the negatively charged counterion position crucial for the visible light sensitivity is different between vertebrate rhodopsin (Glu113) and mollusk and arthropod rhodopsins (Glu181). This can be explained by an evolutionary scenario where vertebrate rhodopsin newly acquired Glu113 as a counterion, which is thought to have led to higher signaling efficiency of vertebrate rhodopsin. However, the detailed evolutionary steps which led to the higher efficiency in vertebrate rhodopsin still remain unknown. Here, we analyzed the xenopsin group, which is phylogenetically distinct from vertebrate rhodopsin and functions in protostome ciliary cells. Xenopsins are blue-sensitive bistable opsins that regulate cAMP signaling. We found that a bistable xenopsin of Leptochiton asellus had Glu113 as a counterion but did not exhibit elevated signaling efficiency. Therefore, our results show that vertebrate rhodopsin and L. asellus xenopsin regulate cyclic nucleotide signaling in ciliary cells and displaced the counterion position from Glu181 to Glu113 via convergent evolution, whereas subsequently only vertebrate rhodopsin elevated its signaling efficiency by acquiring the mono-stable property.
Topics: Animals; Nucleotides, Cyclic; Opsins; Photoreceptor Cells; Rhodopsin; Vertebrates
PubMed: 36001156
DOI: 10.1007/s00018-022-04525-6 -
Current Biology : CB Jul 2022Diverse light-sensing organs (i.e., eyes) have evolved across animals. Interestingly, several subcellular analogs have been found in eukaryotic microbes. All of these... (Review)
Review
Diverse light-sensing organs (i.e., eyes) have evolved across animals. Interestingly, several subcellular analogs have been found in eukaryotic microbes. All of these systems have a common "recipe": a light occluding or refractory surface juxtaposed to a membrane-layer enriched in type I rhodopsins. In the fungi, several lineages have been shown to detect light using a diversity of non-homologous photo-responsive proteins. However, these systems are not associated with an eyespot-like organelle with one exception found in the zoosporic fungus Blastocladiella emersonii (Be).Be possesses both elements of this recipe: an eyespot composed of lipid-filled structures (often called the side-body complex [SBC]), co-localized with a membrane enriched with a gene-fusion protein composed of a type I (microbial) rhodopsin and guanylyl cyclase enzyme domain (CyclOp-fusion protein). Here, we identify homologous pathway components in four Chytridiomycota orders (Chytridiales, Synchytriales, Rhizophydiales, and Monoblepharidiales). To further explore the architecture of the fungal zoospore and its lipid organelles, we reviewed electron microscopy data (e.g., the works of Barr and Hartmann and Reichle and Fuller) and performed fluorescence-microscopy imaging of four CyclOp-carrying zoosporic fungal species, showing the presence of a variety of candidate eyespot-cytoskeletal ultrastructure systems. We then assessed the presence of canonical photoreceptors across the fungi and inferred that the last common fungal ancestor was able to sense light across a range of wavelengths using a variety of systems, including blue-green-light detection. Our data imply, independently of how the fungal tree of life is rooted, that the apparatus for a CyclOp-organelle light perception system was an ancestral feature of the fungi.
Topics: Animals; Blastocladiella; Chytridiomycota; Fungi; Guanylate Cyclase; Lipids; Minocycline; Rhodopsin
PubMed: 35675809
DOI: 10.1016/j.cub.2022.05.034 -
Photochemical & Photobiological... Nov 2015Rhodopsin has been intensively characterized in its role as a visual pigment and G protein-coupled receptor responsible for dim-light vision. We recently discovered that... (Review)
Review
Rhodopsin has been intensively characterized in its role as a visual pigment and G protein-coupled receptor responsible for dim-light vision. We recently discovered that it also functions as an ATP-independent phospholipid scramblase: when reconstituted into large unilamellar vesicles, rhodopsin accelerates the normally sluggish transbilayer translocation of common phospholipids by more than 1000-fold, to rates in excess of 10 000 phospholipids transported per rhodopsin per second. Here we summarize the work leading to this discovery and speculate on the mechanism by which rhodopsin scrambles phospholipids. We also present a hypothesis that rhodopsin's scramblase activity is necessary for the function of the ABC transporter ABCA4 that is responsible for mitigating the toxic accumulation of 11-cis-retinal and bis-retinoids in the retina.
Topics: Animals; Humans; Phospholipids; Rhodopsin
PubMed: 26179029
DOI: 10.1039/c5pp00195a