Rhodopsin
Rhodopsin, also known as visual purple, is a biological 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.[1] Exposed to light, the pigment immediately photobleaches, and it takes about 30 minutes[2] to regenerate fully in humans.
Contents |
[edit] 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, binds retinal (a photoreactive chromophore), which is located in a central pocket on the seventh helix at a lysine residue. Retinal lies horizontally with relation to the membrane. Each outer segment disc contains thousands of 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.[2][3][4]
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.[2]
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.[5][6][7]
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.[8]
[edit] 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.[9] 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.[10] Several other pathological states relating to rhodopsin have been discovered including poor post-Golgi trafficking, dysregulative activation, rod outer segment instability and arrestin binding.[10]
[edit] Microbial rhodopsins
Some prokaryotes express proton pumps called bacteriorhodopsin, proteorhodopsin, xanthorhodopsin to carry out phototrophy.[11] 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.[11] 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 the G-protein coupled receptor (GPCR) family to which rhodopsins belong. Nevertheless, bacterial rhodopsins and GPCR are possibly evolutionarily related, based on the similarity of their three-dimensional structures. Therefore, they have been assigned to the same superfamily in Structural Classification of Proteins.[12]
[edit] References
- ^ Litmann BJ, Mitchell DC (1996). "Rhodopsin structure and function". In Lee AG. Rhodopsin and G-Protein Linked Receptors, Part A (Vol 2, 1996) (2 Vol Set). Greenwich, Conn: JAI Press. pp. 1–32. ISBN 1-55938-659-2.
- ^ a b c Stuart JA, Brige RR (1996). "Characterization of the primary photochemical events in bacteriorhodopsin and rhodopsin". In Lee AG. Rhodopsin and G-Protein Linked Receptors, Part A (Vol 2, 1996) (2 Vol Set). Greenwich, Conn: JAI Press. pp. 33–140. ISBN 1-55938-659-2.
- ^ Hofmann KP, Heck M (1996). "Light-induced protein-protein interactions on the rod photoreceptor disc membrane". In Lee AG. Rhodopsin and G-Protein Linked Receptors, Part A (Vol 2, 1996) (2 Vol Set). Greenwich, Conn: JAI Press. pp. 141–198. ISBN 1-55938-659-2.
- ^ Kolb H, Fernandez E, Nelson R, Jones BW (2010-03-01). "Webvision: Photoreceptors". University of Utah. http://webvision.med.utah.edu/photo1.html.
- ^ Nakamichi H, Okada T (June 2006). "Crystallographic analysis of primary visual photochemistry". Angew. Chem. Int. Ed. Engl. 45 (26): 4270–3. doi:10.1002/anie.200600595. PMID 16586416.
- ^ Schreiber M, Sugihara M, Okada T, Buss V (June 2006). "Quantum mechanical studies on the crystallographic model of bathorhodopsin". Angew. Chem. Int. Ed. Engl. 45 (26): 4274–7. doi:10.1002/anie.200600585. PMID 16729349.
- ^ Weingart O (September 2007). "The twisted C11-C12 bond of the rhodopsin chromophore--a photochemical hot spot". J. Am. Chem. Soc. 129 (35): 10618–9. doi:10.1021/ja071793t. PMID 17691730.
- ^ Chabre M, le Maire M (July 2005). "Monomeric G-protein-coupled receptor as a functional unit". Biochemistry 44 (27): 9395–403. doi:10.1021/bi050720o. PMID 15996094.
- ^ Saliba RS, Munro PM, Luthert PJ, Cheetham ME (15 July 2002). "The cellular fate of mutant rhodopsin: quality control, degradation and aggresome formation". J. Cell. Sci. 115 (Pt 14): 2907–18. PMID 12082151. http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=12082151.
- ^ a b Mendes HF, van der Spuy J, Chapple JP, Cheetham ME (April 2005). "Mechanisms of cell death in rhodopsin retinitis pigmentosa: implications for therapy". Trends Mol Med 11 (4): 177–85. doi:10.1016/j.molmed.2005.02.007. PMID 15823756.
- ^ a b Bryant DA, Frigaard NU (November 2006). "Prokaryotic photosynthesis and phototrophy illuminated". Trends Microbiol. 14 (11): 488–96. doi:10.1016/j.tim.2006.09.001. PMID 16997562.
- ^ http://scop.mrc-lmb.cam.ac.uk/scop/data/scop.b.g.e.b.html.
[edit] 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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. PMID 1539595. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1684283.
- 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.
- 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.
- 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. PMID 1833777. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=52716.
- 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.
- 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. PMID 1862076. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=52109.
- 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.
- 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. PMID 1897520. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1683182.
[edit] External links
 |
Wikimedia Commons has media related to: Rhodopsins |
- 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. http://webvision.med.utah.edu/.
- 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
|
|
|
