G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups []. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence []. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [, , , , ]. GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice []. Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs [].The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [, , ].Retinal pigment epithelium (RPE) hosts a putative GPCR. The RPE-retinalGPCR (RGR) covalently binds all-trans- and 11-cis-retinal after reductionby sodium borohydride []. All-trans-retinal is bound preferentially overthe 11-cis isomer. The human sequence is 86% identical to that of bovineRGR [, ], and a lysine residue, analogous to the retinaldehyde attachmentsite of rhodopsin, is conserved in TM domain 7 []. The human gene, whosestructure is distinct from that of the visual pigment genes, spans 14.8 kband is split into 7 exons []. This suggests that the rgr gene representsthe earliest independent branch of the vertebrate opsin gene family [].Since the RGR gene product preferentially binds all-trans-retinal, it isthought that one of its functions may be to catalyse isomerisation of thechromophore by a retinochrome-like mechanism [].
Visual pigments [, ]are the light-absorbing molecules that mediate vision. They consist of an apoprotein, opsin, covalently linked to the chromophore cis-retinal. Vision is effected through the absorption of a photon by cis-retinal which is isomerised to trans-retinal. This isomerisation leads to a change of conformation of the protein. Opsins are integral membrane proteins with seven transmembrane regions that belong to family 1 of G-protein coupled receptors.In vertebrates four different pigments are generally found. Rod cells, which mediate vision in dim light, contain the pigment rhodopsin. Cone cells, which function in bright light, are responsible for colour vision and contain three or more colour pigments (for example, in mammals: red, blue and green).By contrast with vertebrate rhodopsin, which is found in rod cells, insect photoreceptors are found in the ommatidia that comprise the compound eyes. Each Drosophila eye has 800 ommatidia, each of which contains 8 photoreceptor cells (designated R1-R8): R1-R6 are outer cells, while R7 and R8are inner cells. Opsins RH3 and RH4 are sensitive to UV light [, , ]. In Drosophila, the eye is composed of 800 facets or ommatidia. Each ommatidium contains eight photoreceptor cells (R1-R8): the R1 to R6 cells are outer cells, R7 and R8 inner cells. Each of the three types of cells (R1-R6, R7 and R8) expresses a specific opsin.Proteins evolutionary related to opsins include:Squid retinochrome, also known as retinal photoisomerase, which converts various isomers of retinal into 11-cis retinal.Mammalian opsin 3 (Encephalopsin) that may play a role in encephalic photoreception.Mammalian opsin 4 (Melanopsin) that may mediate regulation of circadian rhythms and acute suppression of pineal melatonin.Mammalian retinal pigment epithelium (RPE) RGR [], a protein that may also act in retinal isomerisation.
Visual pigments [, ]are the light-absorbing molecules that mediate vision. They consist of an apoprotein, opsin, covalently linked to the chromophore cis-retinal. Visionis effected through the absorption of a photon by cis-retinal which is isomerised to trans-retinal. This isomerisation leads to a change of conformation of the protein. Opsins are integral membrane proteins with seven transmembrane regions that belong to family 1 of G-protein coupled receptors.In vertebrates four different pigments are generally found. Rod cells, which mediate vision in dim light, contain the pigment rhodopsin. Cone cells, which function in bright light, are responsible for colour vision and contain three or more colour pigments (for example, in mammals: red, blue and green).By contrast with vertebrate rhodopsin, which is found in rod cells, insect photoreceptors are found in the ommatidia that comprise the compound eyes. Each Drosophila eye has 800 ommatidia, each of which contains 8 photoreceptor cells (designated R1-R8): R1-R6 are outer cells, while R7 and R8are inner cells. Opsins RH3 and RH4 are sensitive to UV light [, , ]. In Drosophila, the eye is composed of 800 facets or ommatidia. Each ommatidium contains eight photoreceptor cells (R1-R8): the R1 to R6 cells are outer cells, R7 and R8 inner cells. Each of the three types of cells (R1-R6, R7 and R8) expresses a specific opsin.Proteins evolutionary related to opsins include:Squid retinochrome, also known as retinal photoisomerase, which converts various isomers of retinal into 11-cis retinal.Mammalian opsin 3 (Encephalopsin) that may play a role in encephalic photoreception.Mammalian opsin 4 (Melanopsin) that may mediate regulation of circadian rhythms and acute suppression of pineal melatonin.Mammalian retinal pigment epithelium (RPE) RGR [], a protein that may also actin retinal isomerisation.The attachment site for retinal in the above proteins is a conserved lysineresidue in the middle of the seventh transmembrane helix.
