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{{otheruses4|the visual rhodopsin of vertebrates|other types of rhodopsin|retinylidene protein}}
{{About|the visual rhodopsin of vertebrates|other types of rhodopsin|retinylidene protein}}
{{Infobox gene}}


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'''Rhodopsin''' (also known as '''visual purple''') is a [[light]]-sensitive [[receptor protein]] involved in [[visual phototransduction]]. It is named after ancient Greek ῥόδον (rhódon) for ''rose'', due to its pinkish color, and ὄψις (ópsis) for ''sight''.<ref name="Perception_2008">{{citation | author = Perception | title = Guest Editorial Essay | edition = | publisher = Perception | location = | year = 2008 | origyear = | pages = 1 | quote = | isbn = | chapter = | doi = | url = | accessdate = }}</ref> Rhodopsin is a [[biological pigment]] found in the [[rod cell|rods]] of the [[retina]] and is a  [[G protein-coupled receptor|G-protein-coupled receptor]] (GPCR). Rhodopsin is extremely sensitive to light, and thus enables vision in low-light conditions.<ref name="Litmann_1996">{{cite book |vauthors=Litmann BJ, Mitchell DC | editor = Lee AG | title = Rhodopsin and G-Protein Linked Receptors, Part A (Vol 2, 1996) (2 Vol Set) | edition = | publisher = JAI Press | location = Greenwich, Conn | year = 1996 | origyear = | pages = 1–32 | quote = | isbn = 1-55938-659-2 | chapter = Rhodopsin structure and function | doi = | url = | accessdate = }}</ref>  When rhodopsin is exposed to light, it immediately [[Photobleaching|photobleaches]]. In humans, it is regenerated fully in about 30 minutes, after which rods are more sensitive.<ref name="Stuart_1996">{{cite book |vauthors=Stuart JA, Brige RR | editor = Lee AG | title = Rhodopsin and G-Protein Linked Receptors, Part A (Vol 2, 1996) (2 Vol Set) | edition = | publisher = JAI Press | location = Greenwich, Conn | year = 1996 | origyear = | pages = 33–140 | quote = | isbn = 1-55938-659-2 | chapter = Characterization of the primary photochemical events in bacteriorhodopsin and rhodopsin | doi = | url = | accessdate = }}</ref>
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Rhodopsin was discovered by [[Franz Christian Boll]] in 1876.<ref>{{cite book|title=Encyclopedia of the Neurological Sciences|url=https://books.google.com/books?id=hfjSVIWViRUC&pg=PA441|date=29 April 2014|publisher=Academic Press|isbn=978-0-12-385158-1|pages=441–}}</ref><ref name="Giese2013">{{cite book|last=Giese|first=Arthur C. | name-list-format = vanc |title=Photophysiology: General Principles; Action of Light on Plants|url=https://books.google.com/books?id=16zSBAAAQBAJ&pg=PA9|access-date=23 September 2015|date=24 September 2013|publisher=Elsevier|isbn=978-1-4832-6227-7|page=9}}</ref> Its amino acid sequence and physical structure were established in the early 1980s by the laboratories of [[Yuri Ovchinnikov (biochemist)|Yuri Ovchinnikov]] in Russia and [[Paul Hargrave]] in the United States.<ref>{{cite journal | vauthors = Hofmann L, Palczewski K | title = The G protein-coupled receptor rhodopsin: a historical perspective | journal = Methods in Molecular Biology | volume = 1271 | pages = 3–18 | date = 2015 | pmid = 25697513 | pmc = 4593475 | doi = 10.1007/978-1-4939-2330-4_1 | publisher = Springer New York | isbn = 9781493923298 }}</ref><ref>{{cite journal | vauthors = Hargrave PA, McDowell JH, Curtis DR, Wang JK, Juszczak E, Fong SL, Rao JK, Argos P | title = The structure of bovine rhodopsin | journal = Biophysics of Structure and Mechanism | volume = 9 | issue = 4 | pages = 235–44 | date = 1983 | pmid = 6342691 | doi = 10.1007/bf00535659 | url = https://doi.org/10.1007/BF00535659 }}</ref><ref>{{Cite journal | vauthors = Ovchinnikov YA, Abdulaev NG, Feigina MY, Artamonov ID, Zolotarev AS, Kostina MB, Bogachuk AS , Miroshnikov AI, Martynov VI | date = January 1982 |title=The Complete Amino-Acid-Sequence of Visual Rhodopsin |url= https://www.researchgate.net/publication/222113364_The_Complete_Amino-Acid-Sequence_of_Visual_Rhodopsin |journal=Bioorganicheskaya Khimiya |volume=8 |pages=1011–& | language = Russian }}</ref><ref name="pmid11133840">{{cite journal | vauthors = Papermaster DS | title = Introducing Paul Hargrave, the 2000 recipient of the Friedenwald award | journal = Investigative Ophthalmology & Visual Science | volume = 42 | issue = 1 | pages = 1–2 | date = January 2001 | pmid = 11133840 | doi = | url = https://iovs.arvojournals.org/article.aspx?articleid=2162741 }}</ref>
{{GNF_Protein_box
| image = Rhodopsin-transducin.png
| image_source = Sensory rhodopsin II (rainbow colored) embedded in a [[lipid bilayer]] (heads red and tails blue) with [[Transducin]] below it. G<sub>t</sub>α is colored red, G<sub>t</sub>β blue, and G<sub>t</sub>γ yellow. There is a bound [[Guanosine diphosphate|GDP]] molecule in the G<sub>t</sub>α-subunit and a bound retinal (black) in the rhodopsin. The [[amino-terminus|N-terminus]] terminus of rhodopsin is red and the [[C-terminus]] blue. Presumed anchoring of transducin to the membrane has been drawn in black.
| PDB = {{PDB2|1eds}}, {{PDB2|1edx}}, {{PDB2|1f88}}, {{PDB2|1gzm}}, {{PDB2|1hzx}}, {{PDB2|1jfp}}, {{PDB2|1l9h}}, {{PDB2|1ln6}}, {{PDB2|1u19}}, {{PDB2|2g87}}, {{PDB2|2hpy}}, {{PDB2|2i35}}, {{PDB2|2i36}}, {{PDB2|2i37}}
| Name = Rhodopsin (opsin 2, rod pigment) (retinitis pigmentosa 4, autosomal dominant)
| HGNCid = 10012
| Symbol = RHO
| AltSymbols =; MGC138309; MGC138311; OPN2; RP4
| OMIM = 180380
| ECnumber =
| Homologene = 68068
| MGIid = 97914
| GeneAtlas_image1 = PBB_GE_RHO_206454_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_RHO_206455_s_at_tn.png
| Function = {{GNF_GO|id=GO:0001584 |text = rhodopsin-like receptor activity}} {{GNF_GO|id=GO:0004872 |text = receptor activity}}
| Component = {{GNF_GO|id=GO:0001750 |text = photoreceptor outer segment}} {{GNF_GO|id=GO:0005886 |text = plasma membrane}} {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}}  
| Process = {{GNF_GO|id=GO:0007186 |text = G-protein coupled receptor protein signaling pathway}} {{GNF_GO|id=GO:0007601 |text = visual perception}} {{GNF_GO|id=GO:0007603 |text = phototransduction, visible light}} {{GNF_GO|id=GO:0016056 |text = rhodopsin mediated signaling}} {{GNF_GO|id=GO:0018298 |text = protein-chromophore linkage}} {{GNF_GO|id=GO:0050896 |text = response to stimulus}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 6010
    | Hs_Ensembl = ENSG00000163914
    | Hs_RefseqProtein = NP_000530
    | Hs_RefseqmRNA = NM_000539
    | Hs_GenLoc_db =
    | Hs_GenLoc_chr = 3
    | Hs_GenLoc_start = 130730172
    | Hs_GenLoc_end = 130736867
    | Hs_Uniprot = P08100
    | Mm_EntrezGene = 212541
    | Mm_Ensembl = ENSMUSG00000030324
    | Mm_RefseqmRNA = NM_145383
    | Mm_RefseqProtein = NP_663358
    | Mm_GenLoc_db =
    | Mm_GenLoc_chr = 6
    | Mm_GenLoc_start = 115897546
    | Mm_GenLoc_end = 115904449
    | Mm_Uniprot = Q8K0D8
  }}
}}


'''Rhodopsin''', also known as '''visual purple''', is expressed in [[metazoan]] [[photoreceptor cells]]. It 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 class of [[G-protein coupled receptor]]s. Rhodopsin is extremely sensitive to light, and enables night-vision. Exposed to white light, the pigment immediately bleaches, and it takes about 30 minutes to regenerate fully in humans.
== Structure ==
Rhodopsin consists of two components, a [[protein molecule]] also called scotopsin and a [[covalent]]ly-bound [[Cofactor (biochemistry)|cofactor]] called [[retinal]]. Scotopsin is an [[opsin]], a light-sensitive [[G protein coupled receptor]] that embeds in the [[lipid bilayer]] of cell membranes using seven protein [[transmembrane domain]]s. These domains form a pocket where the photoreactive [[chromophore]], retinal, lies horizontally to the cell membrane, linked to a [[lysine]] residue in the seventh transmembrane domain of the protein. Thousands of rhodopsin molecules are found in each outer segment disc of the host rod cell. Retinal is produced in the [[retina]] from [[vitamin A]], from dietary [[beta-carotene]]. [[Isomerization]] of 11-''cis''-retinal into all-''trans''-retinal by [[light]] sets off a series of conformational changes ('bleaching') in the opsin, eventually leading it to a form called metarhodopsin II (Meta II), which activates an associated [[G protein]], [[transducin]], to trigger a cyclic [[guanosine monophosphate]] (cGMP) [[second messenger]] cascade.<ref name="Stuart_1996"/><ref name="Hofmann_1996">{{cite book |vauthors=Hofmann KP, Heck M | editor = Lee AG | title = Rhodopsin and G-Protein Linked Receptors, Part A (Vol 2, 1996) (2 Vol Set) | edition = | publisher = JAI Press | location = Greenwich, Conn | year = 1996 | origyear = | pages = 141–198 | quote = | isbn = 1-55938-659-2 | chapter = Light-induced protein-protein interactions on the rod photoreceptor disc membrane | doi = | url = | accessdate = }}</ref><ref>{{cite web | url = http://webvision.med.utah.edu/photo1.html| title = Webvision: Photoreceptors|vauthors=Kolb H, Fernandez E, Nelson R, Jones BW | date = 2010-03-01 | work = | publisher = University of Utah | pages = | archiveurl =https://web.archive.org/web/20000816003659/http://webvision.med.utah.edu/photo1.html| archivedate =2000-08-16| quote = | dead-url = yes| accessdate = }}</ref>


==Structure==
Rhodopsin of the [[rod cell|rod]]s most strongly absorbs green-blue light and, therefore, appears reddish-purple, which is why it is also called "visual purple".<ref>{{cite web|last1=Rogers|first1=Kara | name-list-format = vanc |title=Rhodopsin|url=http://www.britannica.com/science/rhodopsin|website=Encyclopædia Britannica|publisher=Britannica.com|accessdate=30 January 2016}}</ref> It is responsible for ''monochromatic'' vision in the dark.<ref name="Stuart_1996"/>
Rhodopsin consists of two building blocks, an '''[[opsin]]''' [[protein]] called '''scotopsin''' and a reversibly [[covalent]]ly bound [[Cofactor_(biochemistry)|cofactor]], [[retinal]] (retinaldehyde). The structure of rhodopsin consists of a bundle of seven transmembrane helices that surround the photoreactive chromophore, 11-cis retinal.  Retinal, the [[chromophore]] portion of rhodopsin, is made in the [[retina]] from [[Vitamin A]]. [[Isomerization]] of 11-''cis''-retinal into all-''trans''-retinal by [[light]] induces a conformational change in the opsin that activates the associated [[G protein]] and triggers a [[second messenger]] cascade.  


Rhodopsin of the [[rod cell|rod]]s most strongly absorbs green-blue light and therefore appears reddish-purple, which is why it is also called "visual purple". It is responsible for the ''monochromatic'' vision in the dark.
[[Image:Bovine rhodopsin.png|thumb|left|200px|Bovine rhodopsin]]
[[Image:Bovine rhodopsin.png|thumb|left|200px|Bovine rhodopsin]]
Several closely related opsins, the [[photopsin]]s, exist that differ only in a few [[amino acid]]s and in the [[wavelength]]s of light that they absorb most strongly. These  pigments are found in the different types of the [[cone cell]]s of the retina and are the basis of [[color vision]]. Humans have three different other opsins beside rhodopsin, with absorption maxima for yellowish-green (photopsin I), green (photopsin II), and bluish-violet (photopsin III) light.
Several closely related opsins differ only in a few [[amino acid]]s and in the [[wavelength]]s of light that they absorb most strongly. Humans have eight other opsins besides rhodopsin, as well as [[cryptochrome]] (light-sensitive, but not an opsin).<ref name="Terakita2005">{{cite journal | vauthors = Terakita A | title = The opsins | journal = Genome Biology | volume = 6 | issue = 3 | pages = 213 | year = 2005 | pmid = 15774036 | pmc = 1088937 | doi = 10.1186/gb-2005-6-3-213 }}</ref><ref name="FoleyGegear2011">{{cite journal | vauthors = Foley LE, Gegear RJ, Reppert SM | title = Human cryptochrome exhibits light-dependent magnetosensitivity | journal = Nature Communications | volume = 2 | pages = 356 | date = June 2011 | pmid = 21694704 | pmc = 3128388 | doi = 10.1038/ncomms1364 }}</ref>


The photoisomerization of rhodopsin has been studied in detail via [[x-ray crystallography]] on rhodopsin crystals. A first photoproduct called '''photorhodopsin''' forms within 200 [[femtosecond]]s after irradiation followed within [[picosecond]]s by a second one called '''bathorhodopsin''' with distorted all-trans bonds. This intermediate can be trapped and studied at [[cryogenic]] temperatures. Several models (a.o. 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 <ref>''Crystallographic Analysis of Primary Visual Photochemistry'' Hitoshi Nakamichi and Tetsuji Okada [[Angew. Chem. Int. Ed.]] '''2006''', 45, 4270 –4273 {{DOI|10.1002/anie.200600595}}</ref> <ref>''Quantum Mechanical Studies on the Crystallographic Model of Bathorhodopsin'' Marko Schreiber, Minoru Sugihara, Tetsuji Okada, and Volker Buss [[Angew. Chem. Int. Ed.]] '''2006''', 45, 4274 –4277 {{DOI|10.1002/anie.200600585}}</ref> <ref>''The Twisted C11-C12 Bond of the Rhodopsin Chromophores A Photochemical Hot Spot'' Oliver Weingart [[J. Am. Chem. Soc.]] '''2007''', 129, 10618-10619 {{DOI|10.1021/ja071793t}}</ref>.
The [[photopsin]]s are found in the [[cone cell]]s 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 cell]]s and absorbs blue light most strongly.


== Rhodopsin and retinal disease ==
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<sup>+</sup>=CH-).<ref>{{cite journal | vauthors = Bownds D, Wald G | title = Reaction of the rhodopsin chromophore with sodium borohydride | journal = Nature | volume = 205 | pages = 254–7 | date = Jan 1965 | pmid = 14270706 | doi = 10.1038/205254a0 }}</ref> 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.<ref name=WaldNobelPrize>{{cite web|last1=The Nobel Foundation|title=The Nobel Prize in Physiology or Medicine 1967|url=https://www.nobelprize.org/nobel_prizes/medicine/laureates/1967/|website=Nobelprize.org|publisher=Nobel Media AB 2014|accessdate=12 December 2015}}</ref> The photoisomerization dynamics has been subsequently investigated with time-resolved [[IR spectroscopy]] and [[UV/Vis]] spectroscopy. A first photoproduct called '''photorhodopsin''' forms within 200 [[femtosecond]]s after irradiation, followed within [[picosecond]]s 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.<ref>{{cite journal | vauthors = Yoshizawa T, Wald G | title = Pre-lumirhodopsin and the bleaching of visual pigments | journal = Nature | volume = 197 | issue = Mar 30 | pages = 1279–86 | date = March 1963 | pmid = 14002749 | doi = 10.1038/1971279a0 }}</ref> 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.<ref>{{cite journal | vauthors = Matthews RG, Hubbard R, Brown PK, Wald G | title = Tautomeric forms of metarhodopsin | journal = The Journal of General Physiology | volume = 47 | pages = 215–40 | date = November 1963 | pmid = 14080814 | doi=10.1085/jgp.47.2.215 | pmc=2195338}}</ref>
The structure of rhodopsin has been studied in detail via [[x-ray crystallography]] on rhodopsin crystals<ref name="pmid28289214">{{cite journal | vauthors = Gulati S, Jastrzebska B, Banerjee S, Placeres ÁL, Miszta P, Gao S, Gunderson K, Tochtrop GP, Filipek S, Katayama K, Kiser PD, Mogi M, Stewart PL, Palczewski K | title = Photocyclic behavior of rhodopsin induced by an atypical isomerization mechanism | journal = Proceedings of the National Academy of Sciences | volume = 114 | issue = 13 | pages = E2608-15 | date = March 2017 | pmid = 28289214 | doi = 10.1073/pnas.1617446114 }}</ref>. 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.<ref name="pmid16586416">{{cite journal | vauthors = Nakamichi H, Okada T | title = Crystallographic analysis of primary visual photochemistry | journal = Angewandte Chemie | volume = 45 | issue = 26 | pages = 4270–3 | date = June 2006 | pmid = 16586416 | doi = 10.1002/anie.200600595 }}</ref><ref name="pmid16729349">{{cite journal | vauthors = Schreiber M, Sugihara M, Okada T, Buss V | title = Quantum mechanical studies on the crystallographic model of bathorhodopsin | journal = Angewandte Chemie | volume = 45 | issue = 26 | pages = 4274–7 | date = June 2006 | pmid = 16729349 | doi = 10.1002/anie.200600585 }}</ref><ref name="pmid17691730">{{cite journal | vauthors = Weingart O | title = The twisted C11=C12 bond of the rhodopsin chromophore--a photochemical hot spot | journal = Journal of the American Chemical Society | volume = 129 | issue = 35 | pages = 10618–9 | date = September 2007 | pmid = 17691730 | doi = 10.1021/ja071793t }}</ref>


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]] <ref>Saliba, R., Munro, P., Luthert, P., Cheetham, E. 2002 The cellular fate of mutant rhodopsin: quality control, degredation and aggresome formation. ''Journal of Cell Science''. '''115''':2907-2918.</ref>. Other mutations on rhodopsin lead to [[congential stationary night blindness]], mainly due to constitutive activation, when the mutations occur around the chromophore binding pocket of rhodopsin (Mendes et al., 2005). Several other pathological states relating to rhodopsin have been discovered including poor post-Golgi trafficing, dysregulative activation, rod outer segment instability and arrestin binding <ref>Mendes, H., van der Spuy, J., Chapple, P., Cheetham, M. 2005. Mechanisms of cell death in rhodopsin retinitis pigmentosa: implications for therapy. ''Trends in Molecular Medicine''. '''11''':4.</ref>.  
Recent data support that it is a functional monomer, instead of a dimer, which was the paradigm of G-protein-coupled receptors for many years.<ref name="pmid15996094">{{cite journal | vauthors = Chabre M, le Maire M | title = Monomeric G-protein-coupled receptor as a functional unit | journal = Biochemistry | volume = 44 | issue = 27 | pages = 9395–403 | date = July 2005 | pmid = 15996094 | doi = 10.1021/bi050720o }}</ref>
 
== Phototransduction ==
Rhodopsin is an essential G-protein coupled receptor in [[phototransduction]].
 
=== Function ===
The product of light activation, Metarhodopsin II, initiates the [[visual phototransduction]] pathway by stimulating the G protein [[transducin]] (G<sub>t</sub>), resulting in the liberation of its α subunit. This GTP-bound subunit in turn [[cyclic nucleotide phosphodiesterase#Activation by Tα|activates]] [[cyclic nucleotide phosphodiesterase|cGMP phosphodiesterase]]. cGMP phosphodiesterase hydrolyzes (breaks down) [[cyclic guanosine monophosphate|cGMP]], lowering its local concentration so it can no longer activate cGMP-dependent [[cation channel]]s.  This leads to the hyperpolarization of photoreceptor cells, changing the rate at which they release transmitters.
 
=== Deactivation ===
Meta II is deactivated rapidly after activating transducin by [[kinase|rhodopsin kinase]] and [[arrestin]].<ref name="pmid12427735">{{cite journal | vauthors = Heck M, Schädel SA, Maretzki D, Bartl FJ, Ritter E, Palczewski K, Hofmann KP | title = Signaling states of rhodopsin. Formation of the storage form, metarhodopsin III, from active metarhodopsin II | journal = The Journal of Biological Chemistry | volume = 278 | issue = 5 | pages = 3162–9 | date = Jan 2003 | pmid = 12427735 | pmc = 1364529 | doi = 10.1074/jbc.M209675200 }}</ref> 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 is hydrolyzed and becomes Meta III. In the rod outer segment, Meta III decays into separate all-trans-retinal and opsin.<ref name="pmid12427735"/> 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.<ref name="pmid12427735"/>
 
== Retinal disease ==
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]].<ref name="pmid12082151">{{cite journal | vauthors = Saliba RS, Munro PM, Luthert PJ, Cheetham ME | title = The cellular fate of mutant rhodopsin: quality control, degradation and aggresome formation | journal = Journal of Cell Science | volume = 115 | issue = Pt 14 | pages = 2907–18 | date = July 2002 | pmid = 12082151 | url = http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=12082151 }}</ref> 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.<ref name="pmid15823756">{{cite journal | vauthors = Mendes HF, van der Spuy J, Chapple JP, Cheetham ME | title = Mechanisms of cell death in rhodopsin retinitis pigmentosa: implications for therapy | journal = Trends in Molecular Medicine | volume = 11 | issue = 4 | pages = 177–85 | date = April 2005 | pmid = 15823756 | doi = 10.1016/j.molmed.2005.02.007 }}</ref> Several other pathological states relating to rhodopsin have been discovered including poor post-Golgi trafficking, dysregulative activation, rod outer segment instability and arrestin binding.<ref name="pmid15823756"/>


== Microbial rhodopsins ==
== Microbial rhodopsins ==
{{Main|Microbial rhodopsin}}


Some [[prokaryote]]s express [[proton pump]]s called [[bacteriorhodopsin]], [[proteorhodopsin]], [[xanthorhodopsin]] to carry out [[phototrophy]].<ref name=bryant>{{cite journal
Some [[prokaryote]]s express [[proton pump]]s called [[bacteriorhodopsin]]s, [[archaerhodopsin]]s, [[proteorhodopsin]]s, and [[xanthorhodopsin]]s to carry out [[phototrophy]].<ref name="pmid16997562">{{cite journal | vauthors = Bryant DA, Frigaard NU | title = Prokaryotic photosynthesis and phototrophy illuminated | journal = Trends in Microbiology | volume = 14 | issue = 11 | pages = 488–96 | date = November 2006 | pmid = 16997562 | doi = 10.1016/j.tim.2006.09.001 }}</ref> Like animal visual pigments, these contain a retinal chromophore (although it is an all-''trans'', rather than 11-''cis'' form) and have seven [[transmembrane helix|transmembrane alpha helices]]; however, they are not coupled to a G protein. Prokaryotic [[halorhodopsin]]s are light-activated chloride pumps.<ref name="pmid16997562"/> Unicellular flagellate algae contain [[channelrhodopsin]]s that act as light-gated cation channels when expressed in heterologous systems. Many other pro- and eukaryotic organisms (in particular, fungi such as ''Neurospora'') express rhodopsin ion pumps or sensory rhodopsins of yet-unknown function. Very recently, microbial rhodopsins with [[guanylyl cyclase]] activity have been discovered.<ref name="Gao2015">{{cite journal | vauthors = Gao SQ, Nagpal J, Schneider MW, Kozjak-Pavlovic V, Nagel G, Gottschalk A | title = Optogenetic manipulation of cGMP in cells and animals by the tightly light-regulated guanylyl-cyclase opsin CyclOp | journal = Nature Communications | volume = 6 | issue = 8046 | date = July 2015 | doi = 10.1038/ncomms9046 | pmid=26345128 | pmc=4569695}}</ref><ref name="Scheib2015">{{cite journal | vauthors = Scheib U, Stehfest K, Gee CE, Körschen HG, Fudim R, Oertner TG, Hegemann P | title = The rhodopsin-guanylyl cyclase of the aquatic fungus Blastocladiella emersonii enables fast optical control of cGMP signaling | journal = Science Signaling | volume = 8 | issue = 389 | pages = rs8 | date = August 2015 | pmid = 26268609 | doi = 10.1126/scisignal.aab0611 }}</ref><ref>{{cite journal | vauthors = Scheib U, Broser M, Constantin OM, Yang S, Gao S, Mukherjee S, Stehfest K, Nagel G, Gee CE, Hegemann P | display-authors = 6 | title = Rhodopsin-cyclases for photocontrol of cGMP/cAMP and 2.3 Å structure of the adenylyl cyclase domain | language = En | journal = Nature Communications | volume = 9 | issue = 1 | pages = 2046 | date = May 2018 | pmid = 29799525 | pmc = 5967339 | doi = 10.1038/s41467-018-04428-w }}</ref>  While all microbial rhodopsins have significant [[sequence homology]] to one another, they have no detectable sequence homology to the [[G protein-coupled receptor|G-protein-coupled receptor]] (GPCR) family to which animal visual rhodopsins belong. Nevertheless, microbial rhodopsins and GPCRs 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]] (SCOP).<ref name="url_SCOP">{{cite web | url = http://scop.mrc-lmb.cam.ac.uk/scop/data/scop.b.g.e.b.html | title = Superfamily: Bacterial photosystem II reaction centre, L and M subunits | work = SCOP }}</ref>
|author=D.A. Bryant & N.-U. Frigaard
|month=Nov
|year=2006
|title=Prokaryotic photosynthesis and phototrophy illuminated
|journal=Trends Microbiol.
|volume=14
|issue=11
|pages=488
|doi=doi:10.1016/j.tim.2006.09.001
}}</ref> Like rhodopsin, these contain retinal and have seven [[transmembrane helix|transmembrane alpha helices]]; however they are not coupled to a G protein. Bacterial [[halorhodopsin]] is a light-activated chloride pump.<ref name=bryant/> 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]] <ref> http://scop.mrc-lmb.cam.ac.uk/scop/data/scop.b.g.e.b.html.</ref>


== References ==
== References ==
{{reflist|2}}
{{Reflist|33em}}


==Further reading==
== Further reading ==
{{refbegin | 2}}
{{Refbegin|33em}}
{{PBB_Further_reading
* {{cite journal |last=|first=| date = May 1992 |year=| title = On the molecular genetics of retinitis pigmentosa |url=| journal = Science | volume = 256 | issue = 5058 | pages = 804–8 | doi = 10.1126/science.1589761 | pmid = 1589761 |via=| vauthors = Humphries P, Kenna P, Farrar GJ }}
| citations =
* {{cite journal |last=|first=| date = July 1995 |year=| title = Involvement of cGMP and calcium in the photoresponse in vertebrate photoreceptor cells |url=| journal = The Journal of the Florida Medical Association | volume = 82 | issue = 7 | pages = 485–8 | doi = | pmid = 7673885 |via=| vauthors = Edwards SC }}
*{{cite journal | author=Humphries P, Kenna P, Farrar GJ |title=On the molecular genetics of retinitis pigmentosa. |journal=Science |volume=256 |issue= 5058 |pages= 804-8 |year= 1992 |pmid= 1589761 |doi= }}
* {{cite journal |last=|first=| year = 1993 | title = Rhodopsin mutations in autosomal dominant retinitis pigmentosa |url=| journal = Human Mutation | volume = 2 | issue = 4 | pages = 249–55 | doi = 10.1002/humu.1380020403 | pmid = 8401533 |via=| vauthors = al-Maghtheh M, Gregory C, Inglehearn C, Hardcastle A, Bhattacharya S |pmc=52109}}
*{{cite journal | author=Edwards SC |title=Involvement of cGMP and calcium in the photoresponse in vertebrate photoreceptor cells. |journal=The Journal of the Florida Medical Association |volume=82 |issue= 7 |pages= 485-8 |year= 1995 |pmid= 7673885 |doi= }}
* {{cite journal |last=|first=| date = September 2002 |year=| title = The eye photoreceptor protein rhodopsin. Structural implications for retinal disease |url=| journal = FEBS Letters | volume = 528 | issue = 1–3 | pages = 17–22 | doi = 10.1016/S0014-5793(02)03241-6 | pmid = 12297272 |via=| vauthors = Garriga P, Manyosa J }}
*{{cite journal | author=al-Maghtheh M, Gregory C, Inglehearn C, ''et al.'' |title=Rhodopsin mutations in autosomal dominant retinitis pigmentosa. |journal=Hum. Mutat. |volume=2 |issue= 4 |pages= 249-55 |year= 1993 |pmid= 8401533 |doi= 10.1002/humu.1380020403 }}
*
*{{cite journal  | author=Garriga P, Manyosa J |title=The eye photoreceptor protein rhodopsin. Structural implications for retinal disease. |journal=FEBS Lett. |volume=528 |issue= 1-3 |pages= 17-22 |year= 2002 |pmid= 12297272 |doi=  }}
* {{cite journal |last=|first=| date = April 1992 |year=| title = A completed screen for mutations of the rhodopsin gene in a panel of patients with autosomal dominant retinitis pigmentosa |url=| journal = Human Molecular Genetics | volume = 1 | issue = 1 | pages = 41–5 | doi = 10.1093/hmg/1.1.41 | pmid = 1301135 |via=| vauthors = Inglehearn CF, Keen TJ, Bashir R, Jay M, Fitzke F, Bird AC, Crombie A, Bhattacharya S }}
*{{cite journal | author=Mendes HF, van der Spuy J, Chapple JP, Cheetham ME |title=Mechanisms of cell death in rhodopsin retinitis pigmentosa: implications for therapy. |journal=Trends in molecular medicine |volume=11 |issue= 4 |pages= 177-85 |year= 2005 |pmid= 15823756 |doi= 10.1016/j.molmed.2005.02.007 }}
* {{cite journal |last=|first=| date = December 1992 |year=| title = Autosomal dominant retinitis pigmentosa: a novel mutation in the rhodopsin gene in the original 3q linked family |url=| journal = Human Molecular Genetics | volume = 1 | issue = 9 | pages = 769–71 | doi = 10.1093/hmg/1.9.769 | pmid = 1302614 |via=| vauthors = Farrar GJ, Findlay JB, Kumar-Singh R, Kenna P, Humphries MM, Sharpe E, Humphries P }}
*{{cite journal | author=Inglehearn CF, Keen TJ, Bashir R, ''et al.'' |title=A completed screen for mutations of the rhodopsin gene in a panel of patients with autosomal dominant retinitis pigmentosa. |journal=Hum. Mol. Genet. |volume=1 |issue= 1 |pages= 41-5 |year= 1993 |pmid= 1301135 |doi= }}
* {{cite journal |last=|first=| date = October 1992 |year=| title = Constitutively active mutants of rhodopsin |url=| journal = Neuron | volume = 9 | issue = 4 | pages = 719–25 | doi = 10.1016/0896-6273(92)90034-B | pmid = 1356370 |via=| vauthors = Robinson PR, Cohen GB, Zhukovsky EA, Oprian DD }}
*{{cite journal  | author=Farrar GJ, Findlay JB, Kumar-Singh R, ''et al.'' |title=Autosomal dominant retinitis pigmentosa: a novel mutation in the rhodopsin gene in the original 3q linked family. |journal=Hum. Mol. Genet. |volume=1 |issue= 9 |pages= 769-71 |year= 1993 |pmid= 1302614 |doi= }}
* {{cite journal |last=|first=| date = June 1992 |year=| title = Point mutations of rhodopsin gene found in Japanese families with autosomal dominant retinitis pigmentosa (ADRP) |url=| journal = The Japanese Journal of Human Genetics | volume = 37 | issue = 2 | pages = 125–32 | doi = 10.1007/BF01899733 | pmid = 1391967 |via=| vauthors = Fujiki K, Hotta Y, Hayakawa M, Sakuma H, Shiono T, Noro M, Sakuma T, Tamai M, Hikiji K, Kawaguchi R }}
*{{cite journal  | author=Robinson PR, Cohen GB, Zhukovsky EA, Oprian DD |title=Constitutively active mutants of rhodopsin. |journal=Neuron |volume=9 |issue= 4 |pages= 719-25 |year= 1992 |pmid= 1356370 |doi= }}
* {{cite journal |last=|first=| date = November 1992 |year=| title = Transgenic mice with a rhodopsin mutation (Pro23His): a mouse model of autosomal dominant retinitis pigmentosa |url=| journal = Neuron | volume = 9 | issue = 5 | pages = 815–30 | doi = 10.1016/0896-6273(92)90236-7 | pmid = 1418997 |via=| vauthors = Olsson JE, Gordon JW, Pawlyk BS, Roof D, Hayes A, Molday RS, Mukai S, Cowley GS, Berson EL, Dryja TP }}
*{{cite journal | author=Fujiki K, Hotta Y, Hayakawa M, ''et al.'' |title=Point mutations of rhodopsin gene found in Japanese families with autosomal dominant retinitis pigmentosa (ADRP). |journal=Jpn. J. Hum. Genet. |volume=37 |issue= 2 |pages= 125-32 |year= 1992 |pmid= 1391967 |doi= }}
* {{cite journal |last=|first=| date = September 1992 |year=| title = A six-generation family with autosomal dominant retinitis pigmentosa and a rhodopsin gene mutation (arginine-135-leucine) |url=| journal = Ophthalmic Paediatrics and Genetics | volume = 13 | issue = 3 | pages = 145–53 | doi = 10.3109/13816819209046483 | pmid = 1484692 |via=| vauthors = Andréasson S, Ehinger B, Abrahamson M, Fex G }}
*{{cite journal  | author=Olsson JE, Gordon JW, Pawlyk BS, ''et al.'' |title=Transgenic mice with a rhodopsin mutation (Pro23His): a mouse model of autosomal dominant retinitis pigmentosa. |journal=Neuron |volume=9 |issue= 5 |pages= 815-30 |year= 1992 |pmid= 1418997 |doi= }}
* {{cite journal |last=|first=| date = March 1992 |year=| title = Recombination between rhodopsin and locus D3S47 (C17) in rhodopsin retinitis pigmentosa families |url=| journal = American Journal of Human Genetics | volume = 50 | issue = 3 | pages = 590–7 | doi =  | pmc = 1684283 | pmid = 1539595 |via=| vauthors = Inglehearn CF, Lester DH, Bashir R, Atif U, Keen TJ, Sertedaki A, Lindsey J, Jay M, Bird AC, Farrar GJ }}
*{{cite journal  | author=Andréasson S, Ehinger B, Abrahamson M, Fex G |title=A six-generation family with autosomal dominant retinitis pigmentosa and a rhodopsin gene mutation (arginine-135-leucine). |journal=Ophthalmic paediatrics and genetics |volume=13 |issue= 3 |pages= 145-53 |year= 1993 |pmid= 1484692 |doi= }}
* {{cite journal |last=|first=| date = May 1992 |year=| title = Ocular findings associated with a rhodopsin gene codon 106 mutation. Glycine-to-arginine change in autosomal dominant retinitis pigmentosa |url=| journal = Archives of Ophthalmology | volume = 110 | issue = 5 | pages = 646–53 | doi = 10.1001/archopht.1992.01080170068026 | pmid = 1580841 |via=| vauthors = Fishman GA, Stone EM, Gilbert LD, Sheffield VC }}
*{{cite journal  | author=Inglehearn CF, Lester DH, Bashir R, ''et al.'' |title=Recombination between rhodopsin and locus D3S47 (C17) in rhodopsin retinitis pigmentosa families. |journal=Am. J. Hum. Genet. |volume=50 |issue= 3 |pages= 590-7 |year= 1992 |pmid= 1539595 |doi=  }}
* {{cite journal |last=|first=| date = September 1991 |year=| title = Autosomal dominant retinitis pigmentosa: four new mutations in rhodopsin, one of them in the retinal attachment site |url=| journal = Genomics | volume = 11 | issue = 1 | pages = 199–205 | doi = 10.1016/0888-7543(91)90119-Y | pmid = 1765377 |via=| vauthors = Keen TJ, Inglehearn CF, Lester DH, Bashir R, Jay M, Bird AC, Jay B, Bhattacharya SS }}
*{{cite journal  | author=Fishman GA, Stone EM, Gilbert LD, Sheffield VC |title=Ocular findings associated with a rhodopsin gene codon 106 mutation. Glycine-to-arginine change in autosomal dominant retinitis pigmentosa. |journal=Arch. Ophthalmol. |volume=110 |issue= 5 |pages= 646-53 |year= 1992 |pmid= 1580841 |doi= }}
* {{cite journal |last=|first=| date = October 1991 |year=| title = Mutation spectrum of the rhodopsin gene among patients with autosomal dominant retinitis pigmentosa |url=| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 88 | issue = 20 | pages = 9370–4 | doi = 10.1073/pnas.88.20.9370 | pmc = 52716 | pmid = 1833777 |via=| vauthors = Dryja TP, Hahn LB, Cowley GS, McGee TL, Berson EL }}
*{{cite journal | author=Keen TJ, Inglehearn CF, Lester DH, ''et al.'' |title=Autosomal dominant retinitis pigmentosa: four new mutations in rhodopsin, one of them in the retinal attachment site. |journal=Genomics |volume=11 |issue= 1 |pages= 199-205 |year= 1992 |pmid= 1765377 |doi= }}
* {{cite journal |last=|first=| date = October 1991 |year=| title = Pro-347-Arg mutation of the rhodopsin gene in autosomal dominant retinitis pigmentosa |url=| journal = Genomics | volume = 11 | issue = 2 | pages = 468–70 | doi = 10.1016/0888-7543(91)90159-C | pmid = 1840561 |via=| vauthors = Gal A, Artlich A, Ludwig M, Niemeyer G, Olek K, Schwinger E, Schinzel A }}
*{{cite journal  | author=Dryja TP, Hahn LB, Cowley GS, ''et al.'' |title=Mutation spectrum of the rhodopsin gene among patients with autosomal dominant retinitis pigmentosa. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=88 |issue= 20 |pages= 9370-4 |year= 1991 |pmid= 1833777 |doi= }}
* {{cite journal |last=|first=| date = August 1991 |year=| title = Rhodopsin mutations in autosomal dominant retinitis pigmentosa |url=| journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 88 | issue = 15 | pages = 6481–5 | doi = 10.1073/pnas.88.15.6481 | pmc = 52109 | pmid = 1862076 |via=| vauthors = Sung CH, Davenport CM, Hennessey JC, Maumenee IH, Jacobson SG, Heckenlively JR, Nowakowski R, Fishman G, Gouras P, Nathans J }}
*{{cite journal  | author=Gal A, Artlich A, Ludwig M, ''et al.'' |title=Pro-347-Arg mutation of the rhodopsin gene in autosomal dominant retinitis pigmentosa. |journal=Genomics |volume=11 |issue= 2 |pages= 468-70 |year= 1992 |pmid= 1840561 |doi= }}
* {{cite journal |last=|first=| date = September 1991 |year=| title = Retinal function and rhodopsin levels in autosomal dominant retinitis pigmentosa with rhodopsin mutations |url=| journal = American Journal of Ophthalmology | volume = 112 | issue = 3 | pages = 256–71 | doi =  10.1016/s0002-9394(14)76726-1| pmid = 1882937 |via=| vauthors = Jacobson SG, Kemp CM, Sung CH, Nathans J }}
*{{cite journal  | author=Sung CH, Davenport CM, Hennessey JC, ''et al.'' |title=Rhodopsin mutations in autosomal dominant retinitis pigmentosa. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=88 |issue= 15 |pages= 6481-5 |year= 1991 |pmid= 1862076 |doi= }}
* {{cite journal |last=|first=| date = October 1991 |year=| title = Identification of novel rhodopsin mutations associated with retinitis pigmentosa by GC-clamped denaturing gradient gel electrophoresis |url=| journal = American Journal of Human Genetics | volume = 49 | issue = 4 | pages = 699–706 | doi =  | pmc = 1683182 | pmid = 1897520 |via=| vauthors = Sheffield VC, Fishman GA, Beck JS, Kimura AE, Stone EM }}
*{{cite journal  | author=Jacobson SG, Kemp CM, Sung CH, Nathans J |title=Retinal function and rhodopsin levels in autosomal dominant retinitis pigmentosa with rhodopsin mutations. |journal=Am. J. Ophthalmol. |volume=112 |issue= 3 |pages= 256-71 |year= 1991 |pmid= 1882937 |doi= }}
{{Refend}}
*{{cite journal | author=Sheffield VC, Fishman GA, Beck JS, ''et al.'' |title=Identification of novel rhodopsin mutations associated with retinitis pigmentosa by GC-clamped denaturing gradient gel electrophoresis. |journal=Am. J. Hum. Genet. |volume=49 |issue= 4 |pages= 699-706 |year= 1991 |pmid= 1897520 |doi=  }}
}}
{{refend}}


== External links ==
== External links ==
{{Commons category|Rhodopsins}}
* {{MeshName|Rhodopsin}}
* {{cite web | url = http://webvision.med.utah.edu/ | title = Webvision Home Page: The organization of the retina and visual system |vauthors=Kolb H, Fernandez E, Nelson R, Jones BW | date = 2010-03-01 | format = | work = | publisher = University of Utah | pages = | quote = | accessdate = }}
* [http://macromoleculeinsights.com/rhodopsin.php The Rhodopsin Protein]
* [http://macromoleculeinsights.com/rhodopsin.php The Rhodopsin Protein]
* [http://www.blackwellpublishing.com/matthews/rhodopsin.html Photoisomerization of rhodopsin], animation.
* [https://web.archive.org/web/20061005123321/http://www.blackwellpublishing.com/matthews/rhodopsin.html Photoisomerization of rhodopsin], animation.
* [http://www.chm.bris.ac.uk/webprojects2003/rogers/998/Rhoeye.htm Rhodopsin and the eye], summary with pictures.
* [http://www.chm.bris.ac.uk/webprojects2003/rogers/998/Rhoeye.htm Rhodopsin and the eye], summary with pictures.
* {{UMichOPM|families|superfamily|6}} - Calculated spatial positions of rhodopsin-like proteins in membrane
* {{MeshName|Rhodopsin}}


{{commonscat|Rhodopsins}}
{{PDB Gallery|geneid=6010}}
{{G protein-coupled receptors}}
{{G protein-coupled receptors}}
{{Eye proteins}}
{{Eye proteins}}
[[Category:G protein coupled receptors]]
{{Use dmy dates|date=April 2017}}
 
[[Category:G protein-coupled receptors]]
[[Category:Sensory receptors]]
[[Category:Sensory receptors]]
[[Category:Pigments]]
[[Category:Biological pigments]]
[[Category:Eye]]
[[Category:Eye]]
 
[[Category:Genes on human chromosome 3]]
[[cs:Rodopsin]]
[[da:Rhodopsin]]
[[de:Rhodopsin]]
[[es:Rodopsina]]
[[fr:Rhodopsine]]
[[hr:Rodopsin]]
[[it:Rodopsina]]
[[he:אופסין#רודופסין]]
[[lt:Rodopsinas]]
[[nl:Rodopsine]]
[[ja:ロドプシン]]
[[pl:Rodopsyna]]
[[pt:Rodopsina]]
[[ru:Родопсин]]
[[fi:Rodopsiini]]

Latest revision as of 13:54, 16 November 2018

This article is about the visual rhodopsin of vertebrates. For other types of rhodopsin, see retinylidene protein.
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Rhodopsin (also known as visual purple) is a light-sensitive receptor protein involved in visual phototransduction. It is named after ancient Greek ῥόδον (rhódon) for rose, due to its pinkish color, and ὄψις (ópsis) for sight.[1] Rhodopsin is a biological pigment found in the rods of the retina and is a G-protein-coupled receptor (GPCR). Rhodopsin is extremely sensitive to light, and thus enables vision in low-light conditions.[2] When rhodopsin is exposed to light, it immediately photobleaches. In humans, it is regenerated fully in about 30 minutes, after which rods are more sensitive.[3]

Rhodopsin was discovered by Franz Christian Boll in 1876.[4][5] Its amino acid sequence and physical structure were established in the early 1980s by the laboratories of Yuri Ovchinnikov in Russia and Paul Hargrave in the United States.[6][7][8][9]

Structure

Rhodopsin consists of two components, a protein molecule also called scotopsin and a covalently-bound cofactor called retinal. Scotopsin is an opsin, a light-sensitive G protein coupled receptor that embeds in the lipid bilayer of cell membranes using seven protein transmembrane domains. These domains form a pocket where the photoreactive chromophore, retinal, lies horizontally to the cell membrane, linked to a lysine residue in the seventh transmembrane domain of the protein. Thousands of rhodopsin molecules are found in each outer segment disc of the host rod cell. Retinal is produced in the retina from vitamin A, from dietary beta-carotene. Isomerization of 11-cis-retinal into all-trans-retinal by light sets off a series of conformational changes ('bleaching') in the opsin, eventually leading it to a form called metarhodopsin II (Meta II), which activates an associated G protein, transducin, to trigger a cyclic guanosine monophosphate (cGMP) second messenger cascade.[3][10][11]

Rhodopsin of the rods most strongly absorbs green-blue light and, therefore, appears reddish-purple, which is why it is also called "visual purple".[12] It is responsible for monochromatic vision in the dark.[3]

File:Bovine rhodopsin.png
Bovine rhodopsin

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).[13][14]

The photopsins are found in 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.

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-).[15] 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.[16] 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.[17] 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.[18] The structure of rhodopsin has been studied in detail via x-ray crystallography on rhodopsin crystals[19]. 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.[20][21][22]

Recent data support that it is a functional monomer, instead of a dimer, which was the paradigm of G-protein-coupled receptors for many years.[23]

Phototransduction

Rhodopsin is an essential G-protein coupled receptor in phototransduction.

Function

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 activates cGMP 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.

Deactivation

Meta II is deactivated rapidly after activating transducin by rhodopsin kinase and arrestin.[24] 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 is hydrolyzed and becomes Meta III. In the rod outer segment, Meta III decays into separate all-trans-retinal and opsin.[24] 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.[24]

Retinal disease

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.[25] 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.[26] Several other pathological states relating to rhodopsin have been discovered including poor post-Golgi trafficking, dysregulative activation, rod outer segment instability and arrestin binding.[26]

Microbial rhodopsins

Main article: Microbial rhodopsin

Some prokaryotes express proton pumps called bacteriorhodopsins, archaerhodopsins, proteorhodopsins, and xanthorhodopsins to carry out phototrophy.[27] Like animal visual pigments, these contain a retinal chromophore (although it is an all-trans, rather than 11-cis form) and have seven transmembrane alpha helices; however, they are not coupled to a G protein. Prokaryotic halorhodopsins are light-activated chloride pumps.[27] Unicellular flagellate algae contain channelrhodopsins that act as light-gated cation channels when expressed in heterologous systems. Many other pro- and eukaryotic organisms (in particular, fungi such as Neurospora) express rhodopsin ion pumps or sensory rhodopsins of yet-unknown function. Very recently, microbial rhodopsins with guanylyl cyclase activity have been discovered.[28][29][30] While all microbial rhodopsins have significant sequence homology to one another, they have no detectable sequence homology to the G-protein-coupled receptor (GPCR) family to which animal visual rhodopsins belong. Nevertheless, microbial rhodopsins and GPCRs 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 (SCOP).[31]

References

  1. ↑ Perception (2008), Guest Editorial Essay, Perception, p. 1
  2. ↑ 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.
  3. ↑ 3.0 3.1 3.2 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.
  4. ↑ Encyclopedia of the Neurological Sciences. Academic Press. 29 April 2014. pp. 441–. ISBN 978-0-12-385158-1.
  5. ↑ Giese AC (24 September 2013). Photophysiology: General Principles; Action of Light on Plants. Elsevier. p. 9. ISBN 978-1-4832-6227-7. Retrieved 23 September 2015.
  6. ↑ Hofmann L, Palczewski K (2015). "The G protein-coupled receptor rhodopsin: a historical perspective". Methods in Molecular Biology. Springer New York. 1271: 3–18. doi:10.1007/978-1-4939-2330-4_1. ISBN 9781493923298. PMC 4593475. PMID 25697513.
  7. ↑ Hargrave PA, McDowell JH, Curtis DR, Wang JK, Juszczak E, Fong SL, Rao JK, Argos P (1983). "The structure of bovine rhodopsin". Biophysics of Structure and Mechanism. 9 (4): 235–44. doi:10.1007/bf00535659. PMID 6342691.
  8. ↑ Ovchinnikov YA, Abdulaev NG, Feigina MY, Artamonov ID, Zolotarev AS, Kostina MB, Bogachuk AS, Miroshnikov AI, Martynov VI (January 1982). "The Complete Amino-Acid-Sequence of Visual Rhodopsin". Bioorganicheskaya Khimiya (in Russian). 8: 1011–&.
  9. ↑ Papermaster DS (January 2001). "Introducing Paul Hargrave, the 2000 recipient of the Friedenwald award". Investigative Ophthalmology & Visual Science. 42 (1): 1–2. PMID 11133840.
  10. ↑ 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.
  11. ↑ Kolb H, Fernandez E, Nelson R, Jones BW (2010-03-01). "Webvision: Photoreceptors". University of Utah. Archived from the original on 2000-08-16.
  12. ↑ Rogers K. "Rhodopsin". Encyclopædia Britannica. Britannica.com. Retrieved 30 January 2016.
  13. ↑ Terakita A (2005). "The opsins". Genome Biology. 6 (3): 213. doi:10.1186/gb-2005-6-3-213. PMC 1088937. PMID 15774036.
  14. ↑ Foley LE, Gegear RJ, Reppert SM (June 2011). "Human cryptochrome exhibits light-dependent magnetosensitivity". Nature Communications. 2: 356. doi:10.1038/ncomms1364. PMC 3128388. PMID 21694704.
  15. ↑ Bownds D, Wald G (Jan 1965). "Reaction of the rhodopsin chromophore with sodium borohydride". Nature. 205: 254–7. doi:10.1038/205254a0. PMID 14270706.
  16. ↑ The Nobel Foundation. "The Nobel Prize in Physiology or Medicine 1967". Nobelprize.org. Nobel Media AB 2014. Retrieved 12 December 2015.
  17. ↑ Yoshizawa T, Wald G (March 1963). "Pre-lumirhodopsin and the bleaching of visual pigments". Nature. 197 (Mar 30): 1279–86. doi:10.1038/1971279a0. PMID 14002749.
  18. ↑ Matthews RG, Hubbard R, Brown PK, Wald G (November 1963). "Tautomeric forms of metarhodopsin". The Journal of General Physiology. 47: 215–40. doi:10.1085/jgp.47.2.215. PMC 2195338. PMID 14080814.
  19. ↑ Gulati S, Jastrzebska B, Banerjee S, Placeres ÁL, Miszta P, Gao S, Gunderson K, Tochtrop GP, Filipek S, Katayama K, Kiser PD, Mogi M, Stewart PL, Palczewski K (March 2017). "Photocyclic behavior of rhodopsin induced by an atypical isomerization mechanism". Proceedings of the National Academy of Sciences. 114 (13): E2608–15. doi:10.1073/pnas.1617446114. PMID 28289214.
  20. ↑ Nakamichi H, Okada T (June 2006). "Crystallographic analysis of primary visual photochemistry". Angewandte Chemie. 45 (26): 4270–3. doi:10.1002/anie.200600595. PMID 16586416.
  21. ↑ 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. PMID 16729349.
  22. ↑ 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. PMID 17691730.
  23. ↑ 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.
  24. ↑ 24.0 24.1 24.2 Heck M, Schädel SA, Maretzki D, Bartl FJ, Ritter E, Palczewski K, Hofmann KP (Jan 2003). "Signaling states of rhodopsin. Formation of the storage form, metarhodopsin III, from active metarhodopsin II". The Journal of Biological Chemistry. 278 (5): 3162–9. doi:10.1074/jbc.M209675200. PMC 1364529. PMID 12427735.
  25. ↑ Saliba RS, Munro PM, Luthert PJ, Cheetham ME (July 2002). "The cellular fate of mutant rhodopsin: quality control, degradation and aggresome formation". Journal of Cell Science. 115 (Pt 14): 2907–18. PMID 12082151.
  26. ↑ 26.0 26.1 Mendes 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. PMID 15823756.
  27. ↑ 27.0 27.1 Bryant DA, Frigaard NU (November 2006). "Prokaryotic photosynthesis and phototrophy illuminated". Trends in Microbiology. 14 (11): 488–96. doi:10.1016/j.tim.2006.09.001. PMID 16997562.
  28. ↑ Gao SQ, Nagpal J, Schneider MW, Kozjak-Pavlovic V, Nagel G, Gottschalk A (July 2015). "Optogenetic manipulation of cGMP in cells and animals by the tightly light-regulated guanylyl-cyclase opsin CyclOp". Nature Communications. 6 (8046). doi:10.1038/ncomms9046. PMC 4569695. PMID 26345128.
  29. ↑ Scheib U, Stehfest K, Gee CE, Körschen HG, Fudim R, Oertner TG, Hegemann P (August 2015). "The rhodopsin-guanylyl cyclase of the aquatic fungus Blastocladiella emersonii enables fast optical control of cGMP signaling". Science Signaling. 8 (389): rs8. doi:10.1126/scisignal.aab0611. PMID 26268609.
  30. ↑ Scheib U, Broser M, Constantin OM, Yang S, Gao S, Mukherjee S, et al. (May 2018). "Rhodopsin-cyclases for photocontrol of cGMP/cAMP and 2.3 Å structure of the adenylyl cyclase domain". Nature Communications. 9 (1): 2046. doi:10.1038/s41467-018-04428-w. PMC 5967339. PMID 29799525.
  31. ↑ "Superfamily: Bacterial photosystem II reaction centre, L and M subunits". SCOP.

Further reading

External links

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