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Rhodopsin 3D.jpeg
Available structures
PDB Ortholog search: PDBe RCSB
Aliases RHO , CSNBAD1, OPN2, RP4, rhodopsin, Rhodopsin, visual purple
External IDs OMIM: 180380 MGI: 97914 HomoloGene: 68068 GeneCards: RHO
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 3: 129.53 – 129.54 Mb Chr 6: 115.93 – 115.94 Mb
PubMed search [3] [4]
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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. [5] Rhodopsin is a biological pigment found in the rods of the retina and is a G-protein-coupled receptor (GPCR). It belongs to a group of photoswitchable opsins. Rhodopsin is extremely sensitive to light, and thus enables vision in low-light conditions. [6] 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. [7]


Rhodopsin was discovered by Franz Christian Boll in 1876. [8] [9]


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. [7] [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. [7]

Bovine rhodopsin Bovine rhodopsin.png
Bovine rhodopsin
Visual cycle Visual cycle.svg
Visual cycle

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


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


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.


Meta II (metarhodopsin 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 (aporhodopsin) 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

Some prokaryotes express proton pumps called bacteriorhodopsins, archaerhodopsins, proteorhodopsins, heliorhodopsins 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]

Related Research Articles

Retinitis pigmentosa Gradual retinal degeneration leading to progressive sight loss

Retinitis pigmentosa (RP) is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreased peripheral vision. As peripheral vision worsens, people may experience "tunnel vision". Complete blindness is uncommon. Onset of symptoms is generally gradual and often in childhood.

Photoreceptor cell Type of neuroepithelial cell

A photoreceptor cell is a specialized type of neuroepithelial cell found in the retina that is capable of visual phototransduction. The great biological importance of photoreceptors is that they convert light into signals that can stimulate biological processes. To be more specific, photoreceptor proteins in the cell absorb photons, triggering a change in the cell's membrane potential.

Guanylate cyclase Lyase enzyme that synthesizes cGMP from GTP

Guanylate cyclase is a lyase enzyme that converts guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP) and pyrophosphate. It is often part of the G protein signaling cascade that is activated by low intracellular calcium levels and inhibited by high intracellular calcium levels. In response to calcium levels, guanylate cyclase synthesizes cGMP from GTP. cGMP keeps cGMP-gated channels open, allowing for the entry of calcium into the cell.

Retinal Chemical compound

Retinal is a polyene chromophore. Retinal, bound to proteins called opsins, is the chemical basis of visual phototransduction, the light-detection stage of visual perception (vision).

Opsin Class of light-sensitive proteins

Opsins are a group of proteins made light-sensitive via the chromophore retinal found in photoreceptor cells of the retina. Five classical groups of opsins are involved in vision, mediating the conversion of a photon of light into an electrochemical signal, the first step in the visual transduction cascade. Another opsin found in the mammalian retina, melanopsin, is involved in circadian rhythms and pupillary reflex but not in vision.

Visual phototransduction Sensory transduction of the visual system

Visual phototransduction is the sensory transduction of the visual system. It is a process by which light is converted into electrical signals in the rod cells, cone cells and photosensitive ganglion cells of the retina of the eye. This cycle was elucidated by George Wald (1906–1997) for which he received the Nobel Prize in 1967. It is so called "Wald's Visual Cycle" after him.

Rhodopsin kinase is a serine/threonine-specific protein kinase involved in phototransduction. This enzyme catalyses the following chemical reaction:

Retinylidene protein, is a family of proteins that use retinal as a chromophore for light reception. It is the molecular basis for a variety of light-sensing systems from phototaxis in flagellates to eyesight in animals. Retinylidene proteins include all forms of opsin and rhodopsin. While rhodopsin in the narrow sense refers to a dim-light visual pigment found in vertebrates, usually on rod cells, rhodopsin in the broad sense refers any molecule consisting of an opsin and a retinal chromophore in the ground state. When activated by light, the chromophore is isomerized, at which point the molecule as a whole is no longer rhodopsin, but a related molecule such as metarhodopsin. However, it remains a retinylidene protein. The chromophore then separates from the opsin, at which point the bare opsin is a retinylidene protein. Thus, the molecule remains a retinylidene protein throughout the phototransduction cycle.

Photoreceptor cell-specific nuclear receptor

The photoreceptor cell-specific nuclear receptor (PNR), also known as NR2E3, is a protein that in humans is encoded by the NR2E3 gene. PNR is a member of the nuclear receptor super family of intracellular transcription factors.


Peropsin, a visual pigment-like receptor, is a protein that in humans is encoded by the RRH gene.

Retinal G protein coupled receptor

RPE-retinal G protein-coupled receptor also known as RGR-opsin is a protein that in humans is encoded by the RGR gene.

Retinitis pigmentosa GTPase regulator

X-linked retinitis pigmentosa GTPase regulator is a GTPase-binding protein that in humans is encoded by the RPGR gene. The gene is located on the X-chromosome and is commonly associated with X-linked retinitis pigmentosa (XLRP). In photoreceptor cells, RPGR is localized in the connecting cilium which connects the protein-synthesizing inner segment to the photosensitive outer segment and is involved in the modulation of cargo trafficked between the two segments.

Peripherin 2

Peripherin-2 is a protein, that in humans is encoded by the PRPH2 gene. Peripherin-2 is found in the rod and cone cells of the retina of the eye. Defects in this protein result in one form of retinitis pigmentosa, an incurable blindness.

Retinaldehyde-binding protein 1

Retinaldehyde-binding protein 1 (RLBP1) also known as cellular retinaldehyde-binding protein (CRALBP) is a 36-kD water-soluble protein that in humans is encoded by the RLBP1 gene.


Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta is the beta subunit of the protein complex PDE6 that is encoded by the PDE6B gene. PDE6 is crucial in transmission and amplification of visual signal. The existence of this beta subunit is essential for normal PDE6 functioning. Mutations in this subunit are responsible for retinal degeneration such as retinitis pigmentosa or congenital stationary night blindness.

SAG (gene)

S-arrestin is a protein that in humans is encoded by the SAG gene.

<i>NRL</i> (gene) Protein-coding gene in the species Homo sapiens

Neural retina-specific leucine zipper protein is a protein that in humans is encoded by the NRL gene.


Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha is an enzyme that in humans is encoded by the PDE6A gene.

Retinal degeneration (rhodopsin mutation)

Retinal degeneration is a retinopathy which consists in the deterioration of the retina caused by the progressive death of its cells. There are several reasons for retinal degeneration, including artery or vein occlusion, diabetic retinopathy, R.L.F./R.O.P., or disease. These may present in many different ways such as impaired vision, night blindness, retinal detachment, light sensitivity, tunnel vision, and loss of peripheral vision to total loss of vision. Of the retinal degenerative diseases retinitis pigmentosa (RP) is a very important example.

Retinal gene therapy holds a promise in treating different forms of non-inherited and inherited blindness.


  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000163914 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000030324 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Perception (2008), Guest Editorial Essay, Perception, p. 1
  6. Litmann BJ, Mitchell DC (1996). "Rhodopsin structure and function". In Lee AG (ed.). Rhodopsin and G-Protein Linked Receptors, Part A (Vol 2, 1996) (2 Vol Set). Greenwich, Conn: JAI Press. pp. 1–32. ISBN   978-1-55938-659-3.
  7. 1 2 3 Stuart JA, Brige RR (1996). "Characterization of the primary photochemical events in bacteriorhodopsin and rhodopsin". In Lee AG (ed.). Rhodopsin and G-Protein Linked Receptors, Part A (Vol 2, 1996) (2 Vol Set). Greenwich, Conn: JAI Press. pp. 33–140. ISBN   978-1-55938-659-3.
  8. Encyclopedia of the Neurological Sciences. Academic Press. 29 April 2014. pp. 441–. ISBN   978-0-12-385158-1.
  9. 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.
  10. Hofmann KP, Heck M (1996). "Light-induced protein-protein interactions on the rod photoreceptor disc membrane". In Lee AG (ed.). Rhodopsin and G-Protein Linked Receptors, Part A (Vol 2, 1996) (2 Vol Set). Greenwich, Conn: JAI Press. pp. 141–198. ISBN   978-1-55938-659-3.
  11. Kolb H, Fernandez E, Nelson R, Jones BW (1 March 2010). "Webvision: Photoreceptors". University of Utah. Archived from the original on 16 August 2000.
  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. Bibcode:2011NatCo...2..356F. doi:10.1038/ncomms1364. PMC   3128388 . PMID   21694704.
  15. Bownds D, Wald G (January 1965). "Reaction of the rhodopsin chromophore with sodium borohydride". Nature. 205 (4968): 254–7. Bibcode:1965Natur.205..254B. doi:10.1038/205254a0. PMID   14270706. S2CID   4226447.
  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. Bibcode:1963Natur.197.1279Y. doi:10.1038/1971279a0. PMID   14002749. S2CID   4263392.
  18. Matthews RG, Hubbard R, Brown PK, Wald G (November 1963). "Tautomeric forms of metarhodopsin". The Journal of General Physiology. 47 (2): 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 . PMC   5380078 . 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. 1 2 3 Heck M, Schädel SA, Maretzki D, Bartl FJ, Ritter E, Palczewski K, Hofmann KP (January 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. doi:10.1242/jcs.115.14.2907. PMID   12082151.
  26. 1 2 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. 1 2 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): 8046. Bibcode:2015NatCo...6.8046G. 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. S2CID   13140205.
  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. Bibcode:2018NatCo...9.2046S. doi:10.1038/s41467-018-04428-w. PMC   5967339 . PMID   29799525.
  31. "Superfamily: Bacterial photosystem II reaction centre, L and M subunits". SCOP.

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