Rhodopsin

This article is about the visual rhodopsin of vertebrates. For other types of rhodopsin, see retinylidene protein.

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Rhodopsin (opsin 2, rod pigment) (retinitis pigmentosa 4, autosomal dominant)
250px Sensory rhodopsin II (rainbow colored) embedded in a lipid bilayer (heads red and tails blue) with Transducin below it. Gtα is colored red, Gtβ blue, and Gtγ yellow. There is a bound GDP molecule in the Gtα-subunit and a bound retinal (black) in the rhodopsin. The N-terminus terminus of rhodopsin is red and the C-terminus blue. Presumed anchoring of transducin to the membrane has been drawn in black.
Available structures PDB 1eds, 1edx, 1f88, 1gzm, 1hzx, 1jfp, 1l9h, 1ln6, 1u19, 2g87, 2hpy, 2i35, 2i36, 2i37
Identifiers
Symbols	RHO; MGC138309; MGC138311; OPN2; RP4
External IDs	OMIM: 180380 MGI: 97914 HomoloGene: 68068 GeneCards: RHO Gene
Gene Ontology Molecular function • rhodopsin-like receptor activity • receptor activity Cellular component • photoreceptor outer segment • plasma membrane • integral to plasma membrane Biological process • G-protein coupled receptor protein signaling pathway • visual perception • phototransduction, visible light • rhodopsin mediated signaling • protein-chromophore linkage • response to stimulus Sources: Amigo / EGO
RNA expression pattern
250px
250px
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6010	212541
Ensembl	ENSG00000163914	ENSMUSG00000030324
UniProt	P08100	Q8K0D8
RefSeq (mRNA)	NM_000539	NM_145383
RefSeq (protein)	NP_000530	NP_663358
Location (UCSC)	Chr 3: 130.73 - 130.74 Mb	Chr 6: 115.9 - 115.9 Mb
PubMed search	[1]	[2]

Rhodopsin, also known as visual purple, is a pigment of the retina that is responsible for both the formation of the photoreceptor cells and the first events in the perception of light. Rhodopsins belong to the G-protein coupled receptor family and are extremely sensitive to light, enabling vision in low-light conditions. Exposed to light, the pigment immediately photobleaches, and it takes about 30 minutes to regenerate fully in humans.

Structure

Rhodopsin consists of the protein moiety opsin and a reversibly covalently bound cofactor, retinal. Opsin, a bundle of seven transmembrane helices connected to each other by protein loops, totaling, binds retinal, a photoreactive chromophore, in a central pocket on the seventh helix at a lysine residue, which lies horizontally with relation to the membrane. Each outer segment disc, of course, contains many (thousands) visual pigment molecules. About half the opsin is within the lipid bilayer. Retinal is produced in the retina from Vitamin A, from dietary beta-carotene. Isomerization of 11-cis-retinal into all-trans-retinal by light induces a conformational change (bleaching) in opsin continuing with metarhodopsin II, which activates the associated G protein transducin and triggers a second messenger cascade.

Rhodopsin of the rods most strongly absorbs green-blue light and therefore appears reddish-purple, which is why it is also called "visual purple". It is responsible for monochromatic vision in the dark.

File:Bovine rhodopsin.png

Bovine rhodopsin

Several closely related opsins exist that differ only in a few amino acids and in the wavelengths of light that they absorb most strongly. Humans have four different other opsins beside rhodopsin. The photopsins are found in the different types of the cone cells of the retina and are the basis of color vision. They have absorption maxima for yellowish-green (photopsin I), green (photopsin II), and bluish-violet (photopsin III) light. The remaining opsin (melanopsin) is found in photosensitive ganglion cells and absorbs blue light most strongly.

The structure of rhodopsin has been studied in detail via x-ray crystallography on rhodopsin crystals. The photoisomerization dynamics has been investigated with time-resolved IR spectroscopy and UV/Vis spectroscopy. A first photoproduct called photorhodopsin forms within 200 femtoseconds after irradiation followed within picoseconds by a second one called bathorhodopsin with distorted all-trans bonds. This intermediate can be trapped and studied at cryogenic temperatures. Several models (e.g. the bicycle-pedal mechanism, hula-twist mechanism) attempt to explain how the retinal group can change its conformation without clashing with the enveloping rhodopsin protein pocket.

Recent data supports that it is a functional monomer as opposed to a dimer, which was the paradigm of G-coupled protein receptors for many years.

Rhodopsin and retinal disease

Mutation of the rhodopsin gene is a major contributor to various retinopathies such as retinitis pigmentosa. The disease-causing protein generally aggregates with ubiquitin in inclusion bodies, disrupts the intermediate filament network and impairs the ability of the cell to degrade non-functioning proteins which leads to photoreceptor apoptosis. Other mutations on rhodopsin lead to X-linked congenital stationary night blindness, mainly due to constitutive activation, when the mutations occur around the chromophore binding pocket of rhodopsin. Several other pathological states relating to rhodopsin have been discovered including poor post-Golgi trafficking, dysregulative activation, rod outer segment instability and arrestin binding.

Microbial rhodopsins

Main article: Bacterial rhodopsins

Some prokaryotes express proton pumps called bacteriorhodopsin, proteorhodopsin, xanthorhodopsin to carry out phototrophy. Like rhodopsin, these contain retinal and have seven transmembrane alpha helices; however they are not coupled to a G protein. Bacterial halorhodopsin is a light-activated chloride pump. Finally, an alga is known to have an opsin that contains its own monolithic light-gated ion channel, channelrhodopsin. While bacteriorhodopsin, halorhodopsin, and channelrhodopsin all have significant sequence homology to one another, they have no detectable sequence identity to G-protein coupled receptor (GPCR) family where rhodopsins belong. Nevertheless, bacterial rhodopsins and GPCR are possibly evolutionary related, based on similarity of their three-dimensional structures. Therefore, they have been assigned to the same superfamily in Structural Classification of Proteins.

Further reading

• Humphries P, Kenna P, Farrar GJ (1992). "On the molecular genetics of retinitis pigmentosa". Science. 256 (5058): 804–8. doi:10.1126/science.1589761. PMID 1589761. CS1 maint: Multiple names: authors list (link)
• Edwards SC (1995). "Involvement of cGMP and calcium in the photoresponse in vertebrate photoreceptor cells". The Journal of the Florida Medical Association. 82 (7): 485–8. PMID 7673885. 
• al-Maghtheh M, Gregory C, Inglehearn C; et al. (1993). "Rhodopsin mutations in autosomal dominant retinitis pigmentosa". Hum. Mutat. 2 (4): 249–55. doi:10.1002/humu.1380020403. PMID 8401533. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Garriga P, Manyosa J (2002). "The eye photoreceptor protein rhodopsin. Structural implications for retinal disease". FEBS Lett. 528 (1-3): 17–22. doi:10.1016/S0014-5793(02)03241-6. PMID 12297272. 
• Mendes HF, van der Spuy J, Chapple JP, Cheetham ME (2005). "Mechanisms of cell death in rhodopsin retinitis pigmentosa: implications for therapy". Trends in molecular medicine. 11 (4): 177–85. doi:10.1016/j.molmed.2005.02.007. PMID 15823756. CS1 maint: Multiple names: authors list (link)
• Inglehearn CF, Keen TJ, Bashir R; et al. (1993). "A completed screen for mutations of the rhodopsin gene in a panel of patients with autosomal dominant retinitis pigmentosa". Hum. Mol. Genet. 1 (1): 41–5. doi:10.1093/hmg/1.1.41. PMID 1301135. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Farrar GJ, Findlay JB, Kumar-Singh R; et al. (1993). "Autosomal dominant retinitis pigmentosa: a novel mutation in the rhodopsin gene in the original 3q linked family". Hum. Mol. Genet. 1 (9): 769–71. doi:10.1093/hmg/1.9.769. PMID 1302614. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Robinson PR, Cohen GB, Zhukovsky EA, Oprian DD (1992). "Constitutively active mutants of rhodopsin". Neuron. 9 (4): 719–25. doi:10.1016/0896-6273(92)90034-B. PMID 1356370. CS1 maint: Multiple names: authors list (link)
• Fujiki K, Hotta Y, Hayakawa M; et al. (1992). "Point mutations of rhodopsin gene found in Japanese families with autosomal dominant retinitis pigmentosa (ADRP)". Jpn. J. Hum. Genet. 37 (2): 125–32. doi:10.1007/BF01899733. PMID 1391967. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Olsson JE, Gordon JW, Pawlyk BS; et al. (1992). "Transgenic mice with a rhodopsin mutation (Pro23His): a mouse model of autosomal dominant retinitis pigmentosa". Neuron. 9 (5): 815–30. doi:10.1016/0896-6273(92)90236-7. PMID 1418997. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Andréasson S, Ehinger B, Abrahamson M, Fex G (1993). "A six-generation family with autosomal dominant retinitis pigmentosa and a rhodopsin gene mutation (arginine-135-leucine)". Ophthalmic paediatrics and genetics. 13 (3): 145–53. doi:10.3109/13816819209046483. PMID 1484692. CS1 maint: Multiple names: authors list (link)
• Inglehearn CF, Lester DH, Bashir R; et al. (1992). "Recombination between rhodopsin and locus D3S47 (C17) in rhodopsin retinitis pigmentosa families". Am. J. Hum. Genet. 50 (3): 590–7. PMC 1684283 Freely accessible. PMID 1539595. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Fishman GA, Stone EM, Gilbert LD, Sheffield VC (1992). "Ocular findings associated with a rhodopsin gene codon 106 mutation. Glycine-to-arginine change in autosomal dominant retinitis pigmentosa". Arch. Ophthalmol. 110 (5): 646–53. PMID 1580841. CS1 maint: Multiple names: authors list (link)
• Keen TJ, Inglehearn CF, Lester DH; et al. (1992). "Autosomal dominant retinitis pigmentosa: four new mutations in rhodopsin, one of them in the retinal attachment site". Genomics. 11 (1): 199–205. doi:10.1016/0888-7543(91)90119-Y. PMID 1765377. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Dryja TP, Hahn LB, Cowley GS; et al. (1991). "Mutation spectrum of the rhodopsin gene among patients with autosomal dominant retinitis pigmentosa". Proc. Natl. Acad. Sci. U.S.A. 88 (20): 9370–4. doi:10.1073/pnas.88.20.9370. PMC 52716 Freely accessible. PMID 1833777. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Gal A, Artlich A, Ludwig M; et al. (1992). "Pro-347-Arg mutation of the rhodopsin gene in autosomal dominant retinitis pigmentosa". Genomics. 11 (2): 468–70. doi:10.1016/0888-7543(91)90159-C. PMID 1840561. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Sung CH, Davenport CM, Hennessey JC; et al. (1991). "Rhodopsin mutations in autosomal dominant retinitis pigmentosa". Proc. Natl. Acad. Sci. U.S.A. 88 (15): 6481–5. doi:10.1073/pnas.88.15.6481. PMC 52109 Freely accessible. PMID 1862076. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Jacobson SG, Kemp CM, Sung CH, Nathans J (1991). "Retinal function and rhodopsin levels in autosomal dominant retinitis pigmentosa with rhodopsin mutations". Am. J. Ophthalmol. 112 (3): 256–71. PMID 1882937. CS1 maint: Multiple names: authors list (link)
• Sheffield VC, Fishman GA, Beck JS; et al. (1991). "Identification of novel rhodopsin mutations associated with retinitis pigmentosa by GC-clamped denaturing gradient gel electrophoresis". Am. J. Hum. Genet. 49 (4): 699–706. PMC 1683182 Freely accessible. PMID 1897520. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)

External links

• MeSH Rhodopsin
• Kolb H, Fernandez E, Nelson R, Jones BW (2010-03-01). "Webvision Home Page: The organization of the retina and visual system". University of Utah. CS1 maint: Multiple names: authors list (link)
• The Rhodopsin Protein
• Photoisomerization of rhodopsin, animation.
• Rhodopsin and the eye, summary with pictures.
• UMich Orientation of Proteins in Membranes families/superfamily-6 - Calculated spatial positions of rhodopsin-like proteins in membrane

ar:رودوبسين uk:Родопсин