View source for Rhodopsin

{{Short description|Light-sensitive receptor protein}}
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{{About|the visual rhodopsin of the vertebrate [[rod cell|rods]]|other types of rhodopsin|Retinylidene protein}}
{{Use dmy dates|date=April 2017}}
{{Infobox gene}}

'''Rhodopsin''', also known as '''visual purple''', is a [[protein]] encoded by the ''RHO'' [[gene]]<ref name="NCBI">{{cite web|title=RHO rhodopsin [Homo sapiens (human)]|url=https://www.ncbi.nlm.nih.gov/gene/6010|website=NCBI|access-date=November 16, 2017}}</ref> and a [[G-protein-coupled receptor]] (GPCR). It is a [[light]]-sensitive [[receptor protein]] that triggers [[visual phototransduction]] in [[rod cell]]s. Rhodopsin mediates [[scotopic vision|dim light vision]] and thus is extremely sensitive to light.<ref name="Litmann_1996">{{cite book |vauthors=Litmann BJ, Mitchell DC | veditors = Lee AG | title = Rhodopsin and G-Protein Linked Receptors, Part A (Vol 2, 1996) (2 Vol Set) | publisher = JAI Press | location = Greenwich, Conn | year = 1996 | pages = 1–32 | doi = 10.1016/S1874-5342(07)80004-3 | isbn = 978-1-55938-659-3 | chapter = Rhodopsin structure and function | series = Biomembranes: A Multi-Volume Treatise | volume = 2 }}</ref>  When rhodopsin is exposed to light, it immediately [[photobleaching|photobleaches]]. In humans, it is fully regenerated in about 30 minutes, after which the rods are more sensitive.<ref name="Stuart_1996">{{cite book |vauthors=Stuart JA, Brige RR | veditors = Lee AG | title = Rhodopsin and G-Protein Linked Receptors, Part A (Vol 2, 1996) (2 Vol Set) | publisher = JAI Press | location = Greenwich, Conn | year = 1996 | pages = 33–140 | doi = 10.1016/S1874-5342(07)80005-5 | isbn = 978-1-55938-659-3 | chapter = Characterization of the primary photochemical events in bacteriorhodopsin and rhodopsin | series = Biomembranes: A Multi-Volume Treatise | volume = 2 }}</ref> Defects in the rhodopsin gene cause eye diseases such as [[retinitis pigmentosa]] and [[congenital stationary night blindness]].

== History ==
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Expand if you can, the original work of Boll and Kühne should say something about it but also 10.1068/p3711ed (referenced below), Boll's erythropsin
Current meaning: Opsin of the rod cells. Older meaning: Rhodopsin bound with retinal 1 vs poryphopsin (bound with retinal 2), scotopsin and older meaning of opsin (apo-rhodopsin) 
-->
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 | vauthors = Giese AC | 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><ref>{{cite journal | vauthors = Boll F |title = Zur Anatomie und Physiologie der Retina | journal = Archiv für Anatomie und Physiologie, Physiologische Abtheilung | date = 1877 | pages = 4–35 |url = https://books.google.com/books?id=JFwoAQAAIAAJ&pg=PA4 |trans-title= On the anatomy and physiology of the retina | language = German}}</ref> The name rhodopsin derives from [[Ancient Greek]] {{wikt-lang|grc|ῥόδον}} ({{grc-transl|ῥόδον}}) for "rose", due to its pinkish color, and {{wikt-lang|grc|ὄψις}} ({{grc-transl|ὄψις}}) for "sight".<ref>{{cite web |title=Rhodopsin: History and Etymology for rhodopsin |url=https://www.merriam-webster.com/dictionary/rhodopsin |website=Merriam-Webster on-line dictionary}}</ref> It was coined in 1878 by the German physiologist [[Wilhelm Friedrich Kühne]] (1837–1900).<ref>See: 
* ''Merriam-Webster Online Dictionary'':  [https://www.merriam-webster.com/dictionary/rhodopsin Rhodopsin:  History and Etymology for rhodopsin]
* {{cite journal | vauthors = Ewald A, Kühne W |title=Untersuchungen über den Sehpurpur |journal=Untersuchungen aus dem Physiologischen Institute der Universität Heidelberg |date=1878 |volume=1 |pages=139–218 |url=https://www.biodiversitylibrary.org/item/97176#page/189/mode/1up |trans-title=Investigations into rhodopsin |language=German}}  From p. 181:  ''"Was den Sehpurpur im Dunkel ändert, pflegt es z. Th. ''[= zum Theil]'' in derselben Weise zu thun, wie das Licht, d.h. erst eine gelbe Materie, dann farblose Substanz hervorzubringen. Der Kürze wegen und um dem Auslande unsere Bezeichnungen zugänglich zu machen, kann man sagen, Rhodopsin werde erst in Xanthopsin, dieses in Leukopsin zersetzt."'' (That which alters visual purple in the dark usually acts to some extent in the same way as light, that is, first producing a yellow material, then a colorless substance. For the sake of brevity, and in order to make our designations more accessible to foreigners, we can say that rhodopsin is first degraded into xanthopsin [- visual yellow], and [then] this is degraded into leucopsin [- visual white].)</ref><ref>{{cite journal | vauthors = Wade NJ | title = Visual purple (sehpurpur) | journal = Perception | volume = 37 | issue = 11 | pages = 1617–1620 | date = November 2008 | pmid = 19189727 | doi = 10.1068/p3711ed | s2cid = 19145558 | doi-access = free }}</ref>

When [[George Wald]] discovered that rhodopsin is a [[holoprotein]], consisting of [[retinal]] and an [[Apoenzyme#Cofactors|apoprotein]], he called it [[opsin]], which today would be described more narrowly as apo-rhodopsin.<ref>{{cite journal | vauthors = Wald G | title = The photochemical basis of rod vision | journal = Journal of the Optical Society of America | volume = 41 | issue = 12 | pages = 949–956 | date = December 1951 | pmid = 14908734 | doi = 10.1364/josa.41.000949 | bibcode = 1951JOSA...41..949W }}</ref> Today, the term opsin refers more broadly to the class of [[G-protein-coupled receptor]]s that bind retinal and as a result become a light-sensitive [[photoreceptor protein|photoreceptor]], including all closely related proteins.<ref name="Terakita2005" /><ref name=Guehmann2022 /><ref name=Hofmann2022>{{cite journal | vauthors = Hofmann KP, Lamb TD | title = Rhodopsin, light-sensor of vision | journal = Progress in Retinal and Eye Research | volume = 93 | article-number = 101116 | date = March 2023 | pmid = 36273969 | doi = 10.1016/j.preteyeres.2022.101116 | s2cid = 253041556 | doi-access = free }}</ref>{{efn|Hofmann and Lamb<ref name=Hofmann2022 /> use the term opsin in general to mean the group of opsins, however they call apo-rhodopsin in their figure 4 opsin, too.}} When Wald and colleagues later isolated iodopsin from chicken retinas, thereby discovering the first known [[cone opsin]], they called apo-iodopsin ''photopsin'' (for its relation to [[photopic vision]]) and apo-rhodopsin ''scotopsin'' (for its use in [[scotopic vision]]).<ref>{{cite journal | vauthors = Wald G, Brown PK, Smith PH | title = Iodopsin | journal = The Journal of General Physiology | volume = 38 | issue = 5 | pages = 623–681 | date = May 1955 | pmid = 14367777 | pmc = 2147498 | doi = 10.1085/jgp.38.5.623 }}</ref>

== General ==
Rhodopsin is a protein found in the outer segment discs of [[rod cell]]s. It mediates [[scotopic vision]], which is ''monochromatic'' vision in dim light.<ref name="Stuart_1996"/><ref>{{cite web| vauthors = Rogers K  |title=Rhodopsin |url=http://www.britannica.com/science/rhodopsin |website=Encyclopædia Britannica |publisher=Britannica.com |access-date=30 January 2016}}</ref> Rhodopsin most strongly absorbs green-blue light (~500&nbsp;nm)<ref>{{cite journal | vauthors = Wald G, Brown PK | title = Human rhodopsin | journal = Science | volume = 127 | issue = 3292 | pages = 222–226 | date = January 1958 | pmid = 13495499 | doi = 10.1126/science.127.3292.222 | s2cid = 45459123 | bibcode = 1958Sci...127..222W }}</ref><ref>{{cite journal | vauthors = Bowmaker JK, Dartnall HJ | title = Visual pigments of rods and cones in a human retina | journal = The Journal of Physiology | volume = 298 | issue = 1 | pages = 501–511 | date = January 1980 | pmid = 7359434 | pmc = 1279132 | doi = 10.1113/jphysiol.1980.sp013097 }}</ref> and appears therefore reddish-purple, hence the archaic term "visual purple".

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, including rhodopsin, nine opsins,<ref name="Terakita2005">{{cite journal | vauthors = Terakita A | title = The opsins | journal = Genome Biology | volume = 6 | issue = 3 | page = 213 | year = 2005 | pmid = 15774036 | pmc = 1088937 | doi = 10.1186/gb-2005-6-3-213 | doi-access = free }}</ref> as well as [[cryptochrome]] (light-sensitive, but not an opsin).<ref name="FoleyGegear2011">{{cite journal | vauthors = Foley LE, Gegear RJ, Reppert SM | title = Human cryptochrome exhibits light-dependent magnetosensitivity | journal = Nature Communications | volume = 2 | page = 356 | date = June 2011 | pmid = 21694704 | pmc = 3128388 | doi = 10.1038/ncomms1364 | bibcode = 2011NatCo...2..356F }}</ref>

== Structure ==
[[Image:Bovine rhodopsin.png|thumb|left|200px|Cattle rhodopsin]]

Rhodopsin, like other opsins, is a [[G-protein-coupled receptor]] (GPCR).<ref name=Casey1988>{{cite journal | vauthors = Casey PJ, Gilman AG | title = G protein involvement in receptor-effector coupling | journal = The Journal of Biological Chemistry | volume = 263 | issue = 6 | pages = 2577–2580 | date = February 1988 | pmid = 2830256 | doi = 10.1016/s0021-9258(18)69103-3 | s2cid = 38970721 | doi-access = free }}</ref><ref name=Attwood1994>{{cite journal | vauthors = Attwood TK, Findlay JB | title = Fingerprinting G-protein-coupled receptors | journal = Protein Engineering | volume = 7 | issue = 2 | pages = 195–203 | date = February 1994 | pmid = 8170923 | doi = 10.1093/protein/7.2.195 }}</ref> GPCRs are [[chemoreceptor]]s that embed in the [[lipid bilayer]] of the cell membranes and have seven [[transmembrane domain]]s forming a [[binding pocket]] for a ligand.<ref>{{cite journal | vauthors = Dixon RA, Kobilka BK, Strader DJ, Benovic JL, Dohlman HG, Frielle T, Bolanowski MA, Bennett CD, Rands E, Diehl RE, Mumford RA, Slater EE, Sigal IS, Caron MG, Lefkowitz RJ, Strader CD | title = Cloning of the gene and cDNA for mammalian beta-adrenergic receptor and homology with rhodopsin | journal = Nature | volume = 321 | issue = 6065 | pages = 75–79 | date = May 1986 | pmid = 3010132 | doi = 10.1038/321075a0 | s2cid = 4324074 | bibcode = 1986Natur.321...75D }}</ref><ref>{{cite journal | vauthors = Dixon RA, Sigal IS, Rands E, Register RB, Candelore MR, Blake AD, Strader CD | title = Ligand binding to the beta-adrenergic receptor involves its rhodopsin-like core | journal = Nature | volume = 326 | issue = 6108 | pages = 73–77 | date = March 1987 | pmid = 2881211 | doi = 10.1038/326073a0 | s2cid = 4352920 | bibcode = 1987Natur.326...73D }}</ref> The [[ligand]] for rhodopsin is the [[vitamin A]]-based [[chromophore]] 11-''cis''-[[retinal]],<ref>{{cite journal | vauthors = Wald G |title=Carotenoids and the Vitamin A Cycle in Vision |journal=Nature |date=July 1934 |volume=134 |issue=3376 |page=65 |doi=10.1038/134065a0|bibcode=1934Natur.134...65W |s2cid=4022911 |doi-access=free }}</ref><ref>{{cite journal | vauthors = Wald G, Brown PK, Hubbard R, Oroshnik W | title = Hindered Cis Isomers of Vitamin a and Retinene: The Structure of the Neo-B Isomer | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 41 | issue = 7 | pages = 438–451 | date = July 1955 | pmid = 16589696 | pmc = 528115 | doi = 10.1073/pnas.41.7.438 | doi-access = free | bibcode = 1955PNAS...41..438W }}</ref><ref>{{cite journal | vauthors = Brown PK, Wald G | title = The neo-b isomer of vitamin A and retinene | journal = The Journal of Biological Chemistry | volume = 222 | issue = 2 | pages = 865–877 | date = October 1956 | pmid = 13367054 | doi = 10.1016/S0021-9258(20)89944-X | doi-access = free }}</ref><ref>{{cite journal | vauthors = Oroshnik W |title = The Synthesis and Configuration of Neo-B Vitamin A and Neoretinine b | journal = Journal of the American Chemical Society | date = June 1956 | volume = 78 | issue = 11 | pages = 2651–2652 | doi = 10.1021/ja01592a095}}</ref><ref>{{cite journal | vauthors = Oroshnik W, Brown PK, Hubbard R, Wald G | title = HINDERED CIS ISOMERS OF VITAMIN A AND RETINENE: THE STRUCTURE OF THE NEO-b ISOMER | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 42 | issue = 9 | pages = 578–580 | date = September 1956 | pmid = 16589909 | pmc = 534254 | doi = 10.1073/pnas.42.9.578 | doi-access = free | bibcode = 1956PNAS...42..578O }}</ref> which lies horizontally to the cell membrane<ref name=Palczewski2000>{{cite journal | vauthors = Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M | title = Crystal structure of rhodopsin: A G protein-coupled receptor | journal = Science | volume = 289 | issue = 5480 | pages = 739–745 | date = August 2000 | pmid = 10926528 | doi = 10.1126/science.289.5480.739 | citeseerx = 10.1.1.1012.2275 | bibcode = 2000Sci...289..739P }}</ref> and is [[covalent]]ly bound to a [[lysine]] residue (lys296)<ref name=Bownds1965>{{cite journal | vauthors = Bownds D | title = Site of attachment of retinal in rhodopsin | journal = Nature | volume = 216 | issue = 5121 | pages = 1178–1181 | date = December 1967 | pmid = 4294735 | doi = 10.1038/2161178a0 | s2cid = 1657759 | bibcode = 1967Natur.216.1178B }}</ref> in the seventh transmembrane domain<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 = 235–244 | date = 1983 | pmid = 6342691 | doi = 10.1007/BF00535659 | s2cid = 20407577 }}</ref><ref name=Palczewski2000 /> through a [[Schiff-base]].<ref>{{cite journal | vauthors = Collins FD | title = Rhodopsin and indicator yellow | journal = Nature | volume = 171 | issue = 4350 | pages = 469–471 | date = March 1953 | pmid = 13046517 | doi = 10.1038/171469a0 | s2cid = 4152360 | bibcode = 1953Natur.171..469C }}</ref><ref>{{cite journal | vauthors = Pitt GA, Collins FD, Morton RA, Stok P | title = Studies on rhodopsin. VIII. Retinylidenemethylamine, an indicator yellow analogue | journal = The Biochemical Journal | volume = 59 | issue = 1 | pages = 122–128 | date = January 1955 | pmid = 14351151 | pmc = 1216098 | doi = 10.1042/bj0590122 }}</ref> However, 11-''cis''-retinal only blocks the binding pocket and does not activate rhodopsin. It is only activated when 11-''cis''-retinal absorbs a [[photon]] of light and [[Isomerization|isomerizes]] to all-''trans''-retinal,<ref>{{cite journal | vauthors = Hubbard R, Kropf A | title = The Action of Light on Rhodopsin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 44 | issue = 2 | pages = 130–139 | date = February 1958 | pmid = 16590155 | pmc = 335377 | doi = 10.1073/pnas.44.2.130 | doi-access = free | bibcode = 1958PNAS...44..130H }}</ref><ref>{{cite journal | vauthors = Kropf A, Hubbard R | title = The mechanism of bleaching rhodopsin | journal = Annals of the New York Academy of Sciences | volume = 74 | issue = 2 | pages = 266–280 | date = November 1959 | pmid = 13627857 | doi = 10.1111/j.1749-6632.1958.tb39550.x | bibcode = 1959NYASA..74..266K | s2cid = 45830716 }}</ref> the receptor activating form,<ref name=Choe2011>{{cite journal | vauthors = Choe HW, Kim YJ, Park JH, Morizumi T, Pai EF, Krauss N, Hofmann KP, Scheerer P, Ernst OP | title = Crystal structure of metarhodopsin II | journal = Nature | volume = 471 | issue = 7340 | pages = 651–655 | date = March 2011 | pmid = 21389988 | doi = 10.1038/nature09789 | s2cid = 4302421 | bibcode = 2011Natur.471..651C }}</ref><ref name=Wald1968>{{cite journal | vauthors = Wald G | title = Molecular basis of visual excitation | journal = Science | volume = 162 | issue = 3850 | pages = 230–239 | date = October 1968 | pmid = 4877437 | doi = 10.1126/science.162.3850.230 | bibcode = 1968Sci...162..230W }}</ref> causing a configurational change in the rhodopsin,<ref name=Choe2011 /> which activate a [[phototransduction cascade]].<ref name = "Terakita_2012">{{cite journal | vauthors = Terakita A, Kawano-Yamashita E, Koyanagi M |title=Evolution and diversity of opsins |journal=Wiley Interdisciplinary Reviews: Membrane Transport and Signaling |date=January 2012 |volume=1 |issue=1 |pages=104–111 |doi=10.1002/wmts.6|doi-access=free }}</ref> Thus, a chemoreceptor is converted to a [[Photoreceptor protein|light or photo(n)receptor]].<ref name=Guehmann2022>{{cite journal | vauthors = Gühmann M, Porter ML, Bok MJ | title = The Gluopsins: Opsins without the Retinal Binding Lysine | journal = Cells | volume = 11 | issue = 15 | page = 2441 | date = August 2022 | pmid = 35954284 | pmc = 9368030 | doi = 10.3390/cells11152441 | doi-access = free }} [[File:CC-BY icon.svg|50px]] Material was copied and adapted from this source, which is available under a [https://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International License].</ref>

The retinal binding lysine is conserved in almost all opsins, only a few opsins having lost it during [[evolution]].<ref name=Guehmann2022 /> Opsins without the lysine are not light sensitive,<ref name=Katana2019>{{cite journal | vauthors = Katana R, Guan C, Zanini D, Larsen ME, Giraldo D, Geurten BR, Schmidt CF, Britt SG, Göpfert MC | title = Chromophore-Independent Roles of Opsin Apoproteins in Drosophila Mechanoreceptors | journal = Current Biology | volume = 29 | issue = 17 | pages = 2961–2969.e4 | date = September 2019 | pmid = 31447373 | doi = 10.1016/j.cub.2019.07.036 | s2cid = 201420079 | doi-access = free | bibcode = 2019CBio...29E2961K }}</ref><ref name=Leung2020>{{cite journal | vauthors = Leung NY, Thakur DP, Gurav AS, Kim SH, Di Pizio A, Niv MY, Montell C | title = Functions of Opsins in Drosophila Taste | journal = Current Biology | volume = 30 | issue = 8 | pages = 1367–1379.e6 | date = April 2020 | pmid = 32243853 | pmc = 7252503 | doi = 10.1016/j.cub.2020.01.068 | bibcode = 2020CBio...30E1367L }}</ref><ref>{{cite journal | vauthors = Kumbalasiri T, Rollag MD, Isoldi MC, Castrucci AM, Provencio I | title = Melanopsin triggers the release of internal calcium stores in response to light | journal = Photochemistry and Photobiology | volume = 83 | issue = 2 | pages = 273–279 | date = March 2007 | pmid = 16961436 | doi = 10.1562/2006-07-11-RA-964 | s2cid = 23060331 }}</ref> including rhodopsin. Rhodopsin is made [[Receptor (biochemistry)#Constitutive activity|constitutive]]ly (continuously) active by some of those mutations even without light.<ref>{{cite journal | vauthors = Robinson PR, Cohen GB, Zhukovsky EA, Oprian DD | title = Constitutively active mutants of rhodopsin | journal = Neuron | volume = 9 | issue = 4 | pages = 719–725 | date = October 1992 | pmid = 1356370 | doi = 10.1016/0896-6273(92)90034-b | s2cid = 13172583 }}</ref><ref>{{cite journal | vauthors = Yang T, Snider BB, Oprian DD | title = Synthesis and characterization of a novel retinylamine analog inhibitor of constitutively active rhodopsin mutants found in patients with autosomal dominant retinitis pigmentosa | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 25 | pages = 13559–13564 | date = December 1997 | pmid = 9391065 | doi = 10.1073/pnas.94.25.13559 | pmc = 28345 | bibcode = 1997PNAS...9413559Y | doi-access = free }}</ref><ref name="Pharmacology & Therapeutics of Cons">{{cite book | vauthors = Park PS | title = Pharmacology & Therapeutics of Constitutively Active Receptors | chapter = Constitutively active rhodopsin and retinal disease | series = Advances in Pharmacology | volume = 70 | pages = 1–36 | date = 2014 | pmid = 24931191 | doi = 10.1016/B978-0-12-417197-8.00001-8 | pmc = 4120657 | isbn = 978-0-12-417197-8 }}</ref> Also [[wild-type]] rhodopsin is constitutively active, if no 11-''cis''-retinal is bound, but much less.<ref>{{cite journal | vauthors = Melia TJ, Cowan CW, Angleson JK, Wensel TG | title = A comparison of the efficiency of G protein activation by ligand-free and light-activated forms of rhodopsin | journal = Biophysical Journal | volume = 73 | issue = 6 | pages = 3182–3191 | date = December 1997 | pmid = 9414230 | doi = 10.1016/S0006-3495(97)78344-9 | pmc = 1181221 | bibcode = 1997BpJ....73.3182M }}</ref> Therefore 11-''cis''-retinal is an [[inverse agonist]]. Such mutations are one cause of autosomal dominant [[retinitis pigmentosa]].<ref name="Pharmacology & Therapeutics of Cons"/> Artificially, the retinal binding lysine can be shifted to other positions, even into other transmembrane domains, without changing the activity.<ref>{{cite journal | vauthors = Devine EL, Oprian DD, Theobald DL | title = Relocating the active-site lysine in rhodopsin and implications for evolution of retinylidene proteins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 33 | pages = 13351–13355 | date = August 2013 | pmid = 23904486 | doi = 10.1073/pnas.1306826110 | pmc = 3746867 | bibcode = 2013PNAS..11013351D | doi-access = free }}</ref>

The rhodopsin of [[cattle]] has 348 [[amino acid]]s, the retinal binding lysine being Lys296. It was the first [[opsin]] whose [[Protein primary structure|amino acid sequence]]<ref name=Ovchinnikov1982>{{cite journal | vauthors = Ovchinnikov YA | title = Rhodopsin and bacteriorhodopsin: structure-function relationships | journal = FEBS Letters | volume = 148 | issue = 2 | pages = 179–191 | date = November 1982 | pmid = 6759163 | doi = 10.1016/0014-5793(82)80805-3 | s2cid = 85819100 | doi-access = free }}</ref> and [[Protein tertiary structure|3D-structure]] were determined.<ref name=Palczewski2000 /> Its structure has been studied in detail by [[x-ray crystallography]] on rhodopsin crystals.<ref name="Gulati2017">{{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 of the United States of America | volume = 114 | issue = 13 | pages = E2608–E2615 | date = March 2017 | pmid = 28289214 | pmc = 5380078 | doi = 10.1073/pnas.1617446114 | doi-access = free | bibcode = 2017PNAS..114E2608G }}</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 = 4270–4273 | 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 = 4274–4277 | 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 = 10618–10619 | date = September 2007 | pmid = 17691730 | doi = 10.1021/ja071793t }}</ref> 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.<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 = 9395–9403 | date = July 2005 | pmid = 15996094 | doi = 10.1021/bi050720o }}</ref>

Within its native membrane, rhodopsin is found at a high density facilitating its ability to capture photons. Due to its dense packing within the membrane, there is a higher chance of rhodopsin capturing photons. However, the high density also is a disadvantage when it comes to G protein signaling because the needed diffusion becomes more difficult in a crowded membrane that is packed with rhodopsin.<ref>{{cite journal | vauthors = Park PS | title = Rhodopsin Oligomerization and Aggregation | journal = The Journal of Membrane Biology | volume = 252 | issue = 4–5 | pages = 413–423 | date = October 2019 | pmid = 31286171 | doi = 10.1007/s00232-019-00078-1 | pmc = 6790290 }}</ref>

== Phototransduction ==
[[File:Visual cycle.svg|thumb|left|The [[visual cycle]] follows the renewal of the retinal chromophore. It runs in parallel to the phototransduction pathway.]]
Rhodopsin is an essential G-protein coupled receptor in [[phototransduction]].

=== Activation ===
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 name=Bownds1965 /> 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| author = 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|access-date=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 = 1279–1286 | date = March 1963 | pmid = 14002749 | doi = 10.1038/1971279a0 | s2cid = 4263392 | bibcode = 1963Natur.197.1279Y }}</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 | issue = 2 | pages = 215–240 | date = November 1963 | pmid = 14080814 | pmc = 2195338 | doi = 10.1085/jgp.47.2.215 }}</ref>

=== Phototransduction cascade ===
{{main|Visual phototransduction}}

The product of light activation, Metarhodopsin II, initiates the [[visual phototransduction]] [[second messenger]] pathway by stimulating the [[G-protein]] [[transducin]] (G<sub>t</sub>), resulting in the liberation of its α subunit. This [[guanosine triphosphate]] (GTP)-bound subunit in turn [[cyclic nucleotide phosphodiesterase#Activation by Tα|activates]] a [[cyclic nucleotide phosphodiesterase|cGMP phosphodiesterase]]. The 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.<ref name="Hofmann_1996">{{cite book |vauthors=Hofmann KP, Heck M | veditors = Lee AG | title = Rhodopsin and G-Protein Linked Receptors, Part A (Vol 2, 1996) (2 Vol Set) | publisher = JAI Press | location = Greenwich, Conn | year = 1996 | pages = 141–198 | doi = 10.1016/S1874-5342(07)80006-7 | isbn = 978-1-55938-659-3 | chapter = Light-induced protein-protein interactions on the rod photoreceptor disc membrane | series = Biomembranes: A Multi-Volume Treatise | volume = 2 }}</ref><ref name = "Terakita_2012" />

=== Deactivation ===
Meta II (metarhodopsin II) is deactivated rapidly after activating transducin by [[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 = 3162–3169 | date = January 2003 | pmid = 12427735 | pmc = 1364529 | doi = 10.1074/jbc.M209675200 | doi-access = free }}</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 (aporhodopsin) 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"/>

== Diseases of the retina ==
Mutations in the rhodopsin gene contribute majorly to various diseases of the retina such as [[retinitis pigmentosa]]. In general, the defect rhodopsin 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 = 2907–2918 | date = July 2002 | pmid = 12082151 | doi = 10.1242/jcs.115.14.2907 | url = https://discovery.ucl.ac.uk/id/eprint/8441/ }}</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 = 177–185 | 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"/>

== See also ==
* [[Bacteriorhodopsin]], used in some [[halobacteria]] as a light-driven [[proton pump]].

== Explanatory notes ==
{{notelist}}

== References ==
{{Reflist}}

== Further reading ==
{{Refbegin|30em}}
* {{cite journal | vauthors = Humphries P, Kenna P, Farrar GJ | title = On the molecular genetics of retinitis pigmentosa | journal = Science | volume = 256 | issue = 5058 | pages = 804–808 | date = May 1992 | pmid = 1589761 | doi = 10.1126/science.1589761 | bibcode = 1992Sci...256..804H }}
* {{cite journal | vauthors = 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 = 485–488 | date = July 1995 | pmid = 7673885 }}
* {{cite journal | vauthors = al-Maghtheh M, Gregory C, Inglehearn C, Hardcastle A, Bhattacharya S | title = Rhodopsin mutations in autosomal dominant retinitis pigmentosa | journal = Human Mutation | volume = 2 | issue = 4 | pages = 249–255 | year = 1993 | pmid = 8401533 | doi = 10.1002/humu.1380020403 | s2cid = 28459589 | doi-access = free }}
* {{cite journal | vauthors = Garriga P, Manyosa J | title = The eye photoreceptor protein rhodopsin. Structural implications for retinal disease | journal = FEBS Letters | volume = 528 | issue = 1–3 | pages = 17–22 | date = September 2002 | pmid = 12297272 | doi = 10.1016/S0014-5793(02)03241-6 | s2cid = 41860711 | doi-access = free }}
* 
* {{cite journal | vauthors = Inglehearn CF, Keen TJ, Bashir R, Jay M, Fitzke F, Bird AC, Crombie A, Bhattacharya S | title = A completed screen for mutations of the rhodopsin gene in a panel of patients with autosomal dominant retinitis pigmentosa | journal = Human Molecular Genetics | volume = 1 | issue = 1 | pages = 41–45 | date = April 1992 | pmid = 1301135 | doi = 10.1093/hmg/1.1.41 }}
* {{cite journal | vauthors = Farrar GJ, Findlay JB, Kumar-Singh R, Kenna P, Humphries MM, Sharpe E, Humphries P | title = Autosomal dominant retinitis pigmentosa: a novel mutation in the rhodopsin gene in the original 3q linked family | journal = Human Molecular Genetics | volume = 1 | issue = 9 | pages = 769–771 | date = December 1992 | pmid = 1302614 | doi = 10.1093/hmg/1.9.769 }}
* {{cite journal | vauthors = Robinson PR, Cohen GB, Zhukovsky EA, Oprian DD | title = Constitutively active mutants of rhodopsin | journal = Neuron | volume = 9 | issue = 4 | pages = 719–725 | date = October 1992 | pmid = 1356370 | doi = 10.1016/0896-6273(92)90034-B | s2cid = 13172583 }}
* {{cite journal | vauthors = Fujiki K, Hotta Y, Hayakawa M, Sakuma H, Shiono T, Noro M, Sakuma T, Tamai M, Hikiji K, Kawaguchi R | title = Point mutations of rhodopsin gene found in Japanese families with autosomal dominant retinitis pigmentosa (ADRP) | journal = The Japanese Journal of Human Genetics | volume = 37 | issue = 2 | pages = 125–132 | date = June 1992 | pmid = 1391967 | doi = 10.1007/BF01899733 | doi-access = free }}
* {{cite journal | vauthors = Olsson JE, Gordon JW, Pawlyk BS, Roof D, Hayes A, Molday RS, Mukai S, Cowley GS, Berson EL, Dryja TP | title = Transgenic mice with a rhodopsin mutation (Pro23His): a mouse model of autosomal dominant retinitis pigmentosa | journal = Neuron | volume = 9 | issue = 5 | pages = 815–830 | date = November 1992 | pmid = 1418997 | doi = 10.1016/0896-6273(92)90236-7 | s2cid = 37524461 }}
* {{cite journal | vauthors = 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 = 145–153 | date = September 1992 | pmid = 1484692 | doi = 10.3109/13816819209046483 }}
* {{cite journal | vauthors = Inglehearn CF, Lester DH, Bashir R, Atif U, Keen TJ, Sertedaki A, Lindsey J, Jay M, Bird AC, Farrar GJ | title = Recombination between rhodopsin and locus D3S47 (C17) in rhodopsin retinitis pigmentosa families | journal = American Journal of Human Genetics | volume = 50 | issue = 3 | pages = 590–597 | date = March 1992 | pmid = 1539595 | pmc = 1684283 }}
* {{cite journal | vauthors = 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 = Archives of Ophthalmology | volume = 110 | issue = 5 | pages = 646–653 | date = May 1992 | pmid = 1580841 | doi = 10.1001/archopht.1992.01080170068026 }}
* {{cite journal | vauthors = Keen TJ, Inglehearn CF, Lester DH, Bashir R, Jay M, Bird AC, Jay B, Bhattacharya SS | 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 | date = September 1991 | pmid = 1765377 | doi = 10.1016/0888-7543(91)90119-Y }}
* {{cite journal | vauthors = Dryja TP, Hahn LB, Cowley GS, McGee TL, Berson EL | title = Mutation spectrum of the rhodopsin gene among patients with autosomal dominant retinitis pigmentosa | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 88 | issue = 20 | pages = 9370–9374 | date = October 1991 | pmid = 1833777 | pmc = 52716 | doi = 10.1073/pnas.88.20.9370 | doi-access = free | bibcode = 1991PNAS...88.9370D }}
* {{cite journal | vauthors = Gal A, Artlich A, Ludwig M, Niemeyer G, Olek K, Schwinger E, Schinzel A | title = Pro-347-Arg mutation of the rhodopsin gene in autosomal dominant retinitis pigmentosa | journal = Genomics | volume = 11 | issue = 2 | pages = 468–470 | date = October 1991 | pmid = 1840561 | doi = 10.1016/0888-7543(91)90159-C }}
* {{cite journal | vauthors = Sung CH, Davenport CM, Hennessey JC, Maumenee IH, Jacobson SG, Heckenlively JR, Nowakowski R, Fishman G, Gouras P, Nathans J | title = Rhodopsin mutations in autosomal dominant retinitis pigmentosa | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 88 | issue = 15 | pages = 6481–6485 | date = August 1991 | pmid = 1862076 | pmc = 52109 | doi = 10.1073/pnas.88.15.6481 | doi-access = free | bibcode = 1991PNAS...88.6481S }}
* {{cite journal | vauthors = Jacobson SG, Kemp CM, Sung CH, Nathans J | title = Retinal function and rhodopsin levels in autosomal dominant retinitis pigmentosa with rhodopsin mutations | journal = American Journal of Ophthalmology | volume = 112 | issue = 3 | pages = 256–271 | date = September 1991 | pmid = 1882937 | doi = 10.1016/s0002-9394(14)76726-1 | doi-access = free }}
* {{cite journal | vauthors = Sheffield VC, Fishman GA, Beck JS, Kimura AE, Stone EM | title = Identification of novel rhodopsin mutations associated with retinitis pigmentosa by GC-clamped denaturing gradient gel electrophoresis | journal = American Journal of Human Genetics | volume = 49 | issue = 4 | pages = 699–706 | date = October 1991 | pmid = 1897520 | pmc = 1683182 }}
{{Refend}}

== 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 | publisher = University of Utah }}
* {{usurped|1=[https://web.archive.org/web/20071007185020/http://macromoleculeinsights.com/rhodopsin.php The Rhodopsin Protein]}}
* [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] {{Webarchive|url=https://web.archive.org/web/20230331072245/http://www.chm.bris.ac.uk/webprojects2003/rogers/998/Rhoeye.htm |date=31 March 2023 }}, summary with pictures.

{{PDB Gallery|geneid=6010}}
{{G protein-coupled receptors}}
{{Eye proteins}}
{{Authority control}}

[[Category:Biological pigments]]
[[Category:Eye]]
[[Category:G protein-coupled receptors]]
[[Category:Genes on human chromosome 3]]
[[Category:Rhodopsins]]
[[Category:Sensory receptors]]