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Class of light-sensitive proteins From Wikipedia, the free encyclopedia
Animal opsins are G-protein-coupled receptors and a group of proteins made light-sensitive via a chromophore, typically retinal. When bound to retinal, opsins become retinylidene proteins, but are usually still called opsins regardless. Most prominently, they are found in photoreceptor cells of the retina. Five classical groups of opsins are involved in vision, mediating the conversion of a photon of light into an electrochemical signal, the first step in the visual transduction cascade. Another opsin found in the mammalian retina, melanopsin, is involved in circadian rhythms and pupillary reflex but not in vision. Humans have in total nine opsins. Beside vision and light perception, opsins may also sense temperature, sound, or chemicals.
Animal opsins detect light and are the molecules that allow us to see. Opsins are G-protein-coupled receptors (GPCRs),[1][2] which are chemoreceptors and have seven transmembrane domains forming a binding pocket for a ligand.[3][4] The ligand for opsins is the vitamin A-based chromophore 11-cis-retinal,[5][6][7][8][9] which is covalently bound to a lysine residue[10] in the seventh transmembrane domain[11][12][13] through a Schiff-base.[14][15] However, 11-cis-retinal only blocks the binding pocket and does not activate the opsin. The opsin is only activated when 11-cis-retinal absorbs a photon of light and isomerizes to all-trans-retinal,[16][17] the receptor activating form,[18][19] causing conformal changes in the opsin,[18] which activate a phototransduction cascade.[20] Thus, a chemoreceptor is converted to a light or photo(n)receptor.[21]
In the vertebrate photoreceptor cells, all-trans-retinal is released and replaced by a newly synthesized 11-cis-retinal provided from the retinal epithelial cells. Beside 11-cis-retinal (A1), 11-cis-3,4-didehydroretinal (A2) is also found in vertebrates as ligand such as in freshwater fishes.[19] A2-bound opsins have a shifted λmax and absorption spectrum compared to A1-bound opsins.[22]
The seven transmembrane α-helical domains in opsins are connected by three extra-cellular and three cytoplasmic loops. Along the α-helices and the loops, many amino acid residues are highly conserved between all opsin groups, indicating that they serve important functions and thus are called functionally conserved residues. Actually, insertions and deletions in the α-helices are very rare and should preferentially occur in the loops. Therefore, different G-protein-coupled receptors have different length and homologous residues may be in different positions. To make such positions comparable between different receptors, Ballesteros and Weinstein introduced a common numbering scheme for G-protein-coupled receptors.[23] The number before the period is the number of the transmembrane domain. The number after the period is set arbitrarily to 50 for the most conserved residue in that transmembrane domain among GPCRs known in 1995. For instance in the seventh transmembrane domain, the proline in the highly conserved NPxxY7.53 motif is Pro7.50, the asparagine before is then Asp7.49, and the tyrosine three residues after is then Tyr7.53.[21] Another numbering scheme is based on cattle rhodopsin. Cattle rhodopsin has 348 amino acids and is the first opsin whose amino acid sequence[24] and whose 3D-structure were determined.[12] The cattle rhodopsin numbering scheme is widespread in the opsin literature.[21] Therefore, it is useful to use both schemes.
Opsins without the retinal binding lysine are not light sensitive.[25][26] In cattle rhodopsin, this lysine is the 296th amino acid[12][24] and thus according to both numbering schemes Lys2967.43. It is well conserved among opsins, so well conserved that sequences without it were not even considered opsins and thus excluded from large scale phylogenetic reconstructions.[27][28] Even so most opsins have Lys2967.43, some have lost it during evolution: In the nemopsins from nematodes, Lys2967.43 is replaced by Arginine.[29][21] In the astropsins from sea urchins[30][21] and in the gluopsins, Lys2967.43 is replaced by glutamic acid.[21] A nemopsin is expressed in chemosensory cells in Caenorhabditis elegans. Therefore, the nemopsins are thought to be chemoreceptors.[29] The gluopsins are found in insects such as beetles, scorpionflies, dragonflies, and butterflies and moths including model organisms such as the silk moth and the tobacco hawk moth. However, the gluopsins have no known function.[21]
Such function does not need to be light detection, as some opsins are also involved in thermosensation,[31] mechanoreception such as hearing[32] detecting phospholipids, chemosensation, and other functions.[33][34] In particular, the Drosophila rhabdomeric opsins (rhabopsins, r-opsins) Rh1, Rh4, and Rh7 function not only as photoreceptors, but also as chemoreceptors for aristolochic acid. These opsins still have Lys2967.43 like other opsins. However, if this lysine is replaced by an arginine in Rh1, then Rh1 loses light sensitivity but still responds to aristolochic acid. Thus, Lys2967.43 is not needed for Rh1 to function as chemoreceptor.[26] Also the Drosophila rhabopsins Rh1 and Rh6 are involved in mechanoreception, again for mechanoreception Lys2967.43 is not needed, but needed for proper function in the photoreceptor cells.[25]
Beside these functions, an opsin without Lys2967.43, such as a gluopsin, could still be light sensitive, since in cattle rhodopsin, the retinal binding lysine can be shifted from position 296 to other positions, even into other transmembrane domains, without changing light sensitivity.[35]
In the phylogeny above, each clade contains sequences from opsins and other G protein-coupled receptors. The number of sequences and two pie charts are shown next to the clade. The first pie chart shows the percentage of a certain amino acid at the position in the sequences corresponding Lys2967.43 in cattle rhodopsin. The amino acids are color-coded. The colors are red for lysine (K), purple for glutamic acid (E), orange for argenine (R), dark and mid-gray for other amino acids, and light gray for sequences that have no data at that position. The second pie chart gives the taxon composition for each clade, green stands for craniates, dark green for cephalochordates, mid green for echinoderms, brown for nematodes, pale pink for annelids, dark blue for arthropods, light blue for mollusks, and purple for cnidarians. The branches to the clades have pie charts, which give support values for the branches. The values are from right to left SH-aLRT/aBayes/UFBoot. The branches are considered supported when SH-aLRT ≥ 80%, aBayes ≥ 0.95, and UFBoot ≥ 95%. If a support value is above its threshold the pie chart is black otherwise gray.[21]
The NPxxY7.53 motif is well-conserved among opsins and G-protein-coupled receptors. This motif is important for G-protein binding and receptor activation.[21] For instance, if it is mutated to DPxxY7.53 (Asn7.49 → Asp7.49) in the human m3 muscarinic receptor, activation is not affected, but it is abolished if it is mutated to APxxY7.53 (Asn7.49 → Ala7.49).[36] Such a mutation to APxxY7.53 (Asn7.49 → Ala7.49) reduces the G-protein activation of cattle rhodopsin to 45% compared to wild type. Also in cattle rhodopsin, if the motif is mutated to NPxxA7.53 (Tyr7.53 → Ala7.53), cattle rhodopsin does not activate the G-protein.[37] Such a mutation also reduces the activation of the vasopressin V2 receptor. In fact in G-protein-coupled receptors, only loss of function disease mutations are known for Tyr7.53.[38]
Also mutations of Pro7.50 influence G-protein activation, if the motif is mutated to NAxxY7.53 (Pro7.50 → Ala7.50) in the rat m3 muscarinic receptor, the receptor can still be activated but less efficiently,[39] this mutation even abolishes activation in the cholecystokinin B receptor completely.[40] In fact, the RGR-opsins have NAxxY7.53 and retinochromes have VPxxY7.53 for annelids or YPxxY7.53 for mollusks, natively. Both RGR-opsins and retinochromes, belong to the chromopsins.[21] RGR-opsins[41] and retinochromes[42] also bind unlike most opsins all-trans-retinal in the dark and convert it to 11-cis-retinal when illuminated. Therefore, RGR-opsins and retinochromes are thought to neither signal nor activate a phototransduction cascade but to work as photoisomerases to produce 11-cis-retinal for other opsins.[43][44] This view is considered established in the opsin literature,[34][45][43][46][47] even so it has not been shown, conclusively.[21] In fact, the human MT2 melatonin receptor signals via a G-protein and has an NAxxY7.53 motif natively. If this motif is mutated to NPxxY7.53 (Ala7.50 → Pro7.50), the receptor cannot be activated, but can be rescued partially if the motif is mutated to NVxxY7.53 (Ala7.50 → Val7.50).[48] Furthermore, when the motif is mutated to NAxxY7.53 (Pro7.50 → Ala7.50) in cattle rhodopsin, the mutant has 141% of wild type activity.[37] This evidence shows that a GPCR does not need a standard NPxxY7.53 motif for signaling.[21]
Cys138 and Cys110 form a highly conserved disulfide bridge. Glu113 serves as the counterion, stabilizing the protonation of the Schiff linkage between Lys296 and the ligand retinal. The Glu134-Arg135-Tyr136 is another highly conserved motif, involved in the propagation of the transduction signal once a photon has been absorbed.
Certain amino acid residues, termed spectral tuning sites, have a strong effect on λmax values. Using site-directed mutagenesis, it is possible to selectively mutate these residues and investigate the resulting changes in light absorption properties of the opsin. It is important to differentiate spectral tuning sites, residues that affect the wavelength at which the opsin absorbs light, from functionally conserved sites, residues important for the proper functioning of the opsin. They are not mutually exclusive, but, for practical reasons, it is easier to investigate spectral tuning sites that do not affect opsin functionality. For a comprehensive review of spectral tuning sites see Yokoyama[49] and Deeb.[50] The impact of spectral tuning sites on λmax differs between different opsin groups and between opsin groups of different species.
Abbr. | Name | λmax | Color | Eye | Brain | Skin | Chromosomal location[44] |
---|---|---|---|---|---|---|---|
OPN1LW | L-cone (red-cone) opsin | 557 nm | Yellow | Cone | — | — | Xq28[44] |
OPN1MW | M-cone (green-cone) opsin | 527 nm | Green | Cone | — | — | Xq28[44] |
OPN1SW | S-cone (blue-cone) opsin | 420 nm | Violet | Cone | — | Melanocytes, keratinocytes[51] | 7q32.1[44] |
OPN2 (RHO) | Rhodopsin | 505 nm | Blue–green | Rod | — | Melanocytes, keratinocytes[51] | 3q22.1[44] |
OPN3 | Encephalopsin, panopsin | S-M | Blue–green | Rod, cone, OPL, IPL, GCL[52] | Cerebral cortex, cerebellum, striatum, thalamus, hypothalamus[53][54] | Melanocytes, keratinocytes[51] | 1q43[44] |
OPN4 | Melanopsin | 480 nm[55] | Sky blue | ipRGC[55] | — | — | 10q23.2[44] |
OPN5 | Neuropsin | 380 nm[56] | Ultraviolet[56] | Neural retina, RPE[57] | Anterior hypothalamus[58] | Melanocytes, keratinocytes[51] | 6p12.3[44] |
RRH | Peropsin | RPE cells - microvilli | — | — | 4q25[44] | ||
RGR | Retinal G protein coupled receptor | RPE cells | — | — | 10q23.1[44] |
RPE, retinal pigment epithelium; ipRGC, intrinsically photosensitive retinal ganglion cells; OPL, outer plexiform layer; IPL, inner plexiform layer; GCL, ganglion cell layer
Cuttlefish and octopuses contain opsin in their skin as part of the chromophores. The opsin is part of the sensing network detecting the colour and shape of the cuttlefish's surroundings.[59][60][61]
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