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.
Several closely related opsins differ only in a few amino acids and in the wavelengths of light that they absorb most strongly. Humans have eight other opsins besides rhodopsin, as well as cryptochrome (light-sensitive, but not an opsin).
In rhodopsin, the aldehyde group of retinal is covalently linked to the amino group of a lysine residue on the protein in a protonated Schiff base (-NH+=CH-). When rhodopsin absorbs light, its retinal cofactor isomerizes from the 11-cis to the all-trans configuration, and the protein subsequently undergoes a series of relaxations to accommodate the altered shape of the isomerized cofactor. The intermediates formed during this process were first investigated in the laboratory of George Wald, who received the Nobel prize for this research in 1967. The photoisomerization dynamics has been subsequently 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, and was initially referred to as prelumirhodopsin. In subsequent intermediates lumirhodopsin and metarhodopsin I, the Schiff's base linkage to all-trans retinal remains protonated, and the protein retains its reddish color. The critical change that initiates the neuronal excitation involves the conversion of metarhodopsin I to metarhodopsin II, which is associated with deprotonation of the Schiff's base and change in color from red to yellow.
The structure of rhodopsin has been studied in detail via x-ray crystallography on rhodopsin crystals. 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 support that rhodopsin is a functional monomer, instead of a dimer, which was the paradigm of G-protein-coupled receptors for many years.
The product of light activation, Metarhodopsin II, initiates the visual phototransduction pathway by stimulating the G protein transducin (Gt), resulting in the liberation of its α subunit. This GTP-bound subunit in turn activatescGMP phosphodiesterase. cGMP phosphodiesterase hydrolyzes (breaks down) cGMP, lowering its local concentration so it can no longer activate cGMP-dependent cation channels. This leads to the hyperpolarization of photoreceptor cells, changing the rate at which they release transmitters.
Meta II (metarhodopsin II) is deactivated rapidly after activating transducin by rhodopsin kinase and arrestin. Rhodopsin pigment must be regenerated for further phototransduction to occur. This means replacing all-trans-retinal with 11-cis-retinal and the decay of Meta II is crucial in this process. During the decay of Meta II, the Schiff base link that normally holds all-trans-retinal and the apoprotein opsin (aporhodopsin) is hydrolyzed and becomes Meta III. In the rod outer segment, Meta III decays into separate all-trans-retinal and opsin. A second product of Meta II decay is an all-trans-retinal opsin complex in which the all-trans-retinal has been translocated to second binding sites. Whether the Meta II decay runs into Meta III or the all-trans-retinal opsin complex seems to depend on the pH of the reaction. Higher pH tends to drive the decay reaction towards Meta III.
Mutation of the rhodopsin gene is a major contributor to various retinopathies such as retinitis pigmentosa. In general, the disease-causing protein 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.
^Perception (2008), Guest Editorial Essay, Perception, p. 1
^Litmann BJ, Mitchell DC (1996). "Rhodopsin structure and function". In Lee AG (ed.). Rhodopsin and G-Protein Linked Receptors, Part A (Vol 2, 1996) (2 Vol Set). Greenwich, Conn: JAI Press. pp. 1–32. ISBN978-1-55938-659-3.
^ abcStuart JA, Brige RR (1996). "Characterization of the primary photochemical events in bacteriorhodopsin and rhodopsin". In Lee AG (ed.). Rhodopsin and G-Protein Linked Receptors, Part A (Vol 2, 1996) (2 Vol Set). Greenwich, Conn: JAI Press. pp. 33–140. ISBN978-1-55938-659-3.
^Hofmann KP, Heck M (1996). "Light-induced protein-protein interactions on the rod photoreceptor disc membrane". In Lee AG (ed.). Rhodopsin and G-Protein Linked Receptors, Part A (Vol 2, 1996) (2 Vol Set). Greenwich, Conn: JAI Press. pp. 141–198. ISBN978-1-55938-659-3.
^Schreiber M, Sugihara M, Okada T, Buss V (June 2006). "Quantum mechanical studies on the crystallographic model of bathorhodopsin". Angewandte Chemie. 45 (26): 4274–7. doi:10.1002/anie.200600585. PMID16729349.
^Weingart O (September 2007). "The twisted C11=C12 bond of the rhodopsin chromophore--a photochemical hot spot". Journal of the American Chemical Society. 129 (35): 10618–9. doi:10.1021/ja071793t. PMID17691730.
^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. PMID15996094.
^ abMendes HF, van der Spuy J, Chapple JP, Cheetham ME (April 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. PMID15823756.
Edwards SC (July 1995). "Involvement of cGMP and calcium in the photoresponse in vertebrate photoreceptor cells". The Journal of the Florida Medical Association. 82 (7): 485–8. PMID7673885.
al-Maghtheh M, Gregory C, Inglehearn C, Hardcastle A, Bhattacharya S (1993). "Rhodopsin mutations in autosomal dominant retinitis pigmentosa". Human Mutation. 2 (4): 249–55. doi:10.1002/humu.1380020403. PMID8401533.
Inglehearn CF, Keen TJ, Bashir R, Jay M, Fitzke F, Bird AC, Crombie A, Bhattacharya S (April 1992). "A completed screen for mutations of the rhodopsin gene in a panel of patients with autosomal dominant retinitis pigmentosa". Human Molecular Genetics. 1 (1): 41–5. doi:10.1093/hmg/1.1.41. PMID1301135.
Farrar GJ, Findlay JB, Kumar-Singh R, Kenna P, Humphries MM, Sharpe E, Humphries P (December 1992). "Autosomal dominant retinitis pigmentosa: a novel mutation in the rhodopsin gene in the original 3q linked family". Human Molecular Genetics. 1 (9): 769–71. doi:10.1093/hmg/1.9.769. PMID1302614.
Olsson JE, Gordon JW, Pawlyk BS, Roof D, Hayes A, Molday RS, Mukai S, Cowley GS, Berson EL, Dryja TP (November 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. PMID1418997.
Andréasson S, Ehinger B, Abrahamson M, Fex G (September 1992). "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. PMID1484692.
Fishman GA, Stone EM, Gilbert LD, Sheffield VC (May 1992). "Ocular findings associated with a rhodopsin gene codon 106 mutation. Glycine-to-arginine change in autosomal dominant retinitis pigmentosa". Archives of Ophthalmology. 110 (5): 646–53. doi:10.1001/archopht.1992.01080170068026. PMID1580841.
Keen TJ, Inglehearn CF, Lester DH, Bashir R, Jay M, Bird AC, Jay B, Bhattacharya SS (September 1991). "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. PMID1765377.
Gal A, Artlich A, Ludwig M, Niemeyer G, Olek K, Schwinger E, Schinzel A (October 1991). "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. PMID1840561.
Jacobson SG, Kemp CM, Sung CH, Nathans J (September 1991). "Retinal function and rhodopsin levels in autosomal dominant retinitis pigmentosa with rhodopsin mutations". American Journal of Ophthalmology. 112 (3): 256–71. doi:10.1016/s0002-9394(14)76726-1. PMID1882937.