Rhodopsin

Rhodopsin, also known as visual purple, from Ancient Greek ῥόδον (rhódon, “rose”), due to its pinkish color, and ὄψις (ópsis, “sight”), is a light-sensitive receptor protein. It is a is_associated_with::biological pigment in is_associated_with::photoreceptor cells of the is_associated_with::retina. Rhodopsin is the primary pigment found in rod photoreceptors. Rhodopsins belong to the G-protein-coupled receptor (GPCR) family. They are extremely sensitive to light, enabling vision in low-light conditions. Exposed to light, the pigment immediately photobleaches, and it takes about 45 minutes to regenerate fully in humans.

Its discovery was reported by German physiologist is_associated_with::Franz Christian Boll in 1876.

Structure
Rhodopsin consists of the protein moiety is_associated_with::opsin and a reversibly is_associated_with::covalently bound cofactor, is_associated_with::retinal. Opsin, a bundle of seven transmembrane helices connected to each other by polypeptide loops, binds retinal (a photoreactive is_associated_with::chromophore), which is located in a central pocket on the seventh helix at a is_associated_with::lysine residue. The retinal lies horizontally with relation to the membrane. Each outer segment disc contains thousands of visual pigment molecules. About half the opsin is embedded within the is_associated_with::lipid bilayer. is_associated_with::Retinol is produced in the is_associated_with::retina from is_associated_with::Vitamin A, from dietary is_associated_with::beta-carotene. is_associated_with::Isomerization of 11-cis-retinal into all-trans-retinal by is_associated_with::light induces a conformational change (bleaching) in opsin, continuing with metarhodopsin II, which activates the associated is_associated_with::G protein is_associated_with::transducin and triggers a Cyclic Guanosine Monophosphate, is_associated_with::second messenger, cascade.

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

Several closely related opsins exist that differ only in a few is_associated_with::amino acids and in the is_associated_with::wavelengths of light that they absorb most strongly. Humans have four different other opsins besides rhodopsin. The is_associated_with::photopsins are found in the different types of the is_associated_with::cone cells of the retina and are the basis of is_associated_with::color vision. They have absorption maxima for yellowish-green (photopsin I), green (photopsin II), and bluish-violet (photopsin III) light. The remaining opsin (is_associated_with::melanopsin) is found in is_associated_with::photosensitive ganglion cells and absorbs blue light most strongly.

In rhodopsin, the aldehyde of retinal is covalently linked to the amino group of a lysine residue on the protein in a protonated is_associated_with::Schiff base (-NH+=CH-). When rhodopsin absorbs light, its retinal cofactor isomerizes from the 11-cis to the all-trans configuration, and the protein subsequently undergoes a series of relaxations to accommodate the altered shape of the isomerized cofactor. The intermediates formed during this process were first investigated in the laboratory of George Wald, who received the Nobel prize for this research in 1967. The photoisomerization dynamics has been subsequently investigated with time-resolved is_associated_with::IR spectroscopy and is_associated_with::UV/Vis spectroscopy. A first photoproduct called photorhodopsin forms within 200 is_associated_with::femtoseconds after irradiation, followed within is_associated_with::picoseconds by a second one called bathorhodopsin with distorted all-trans bonds. This intermediate can be trapped and studied at is_associated_with::cryogenic temperatures, and was initially referred to as prelumirhodopsin. In subsequent intermediates lumirhodopsin and metarhodopsin I, the Schiff's base linkage to all-trans retinal remains protonated, and the protein retains its reddish color. The critical change that initiates the neuronal excitation involves the conversion of metarhodopsin I to metarhodopsin II, which is associated with deprotonation of the Schiff's base and change in color from red to yellow. The structure of rhodopsin has been studied in detail via is_associated_with::x-ray crystallography on rhodopsin crystals. Several models (e.g., the bicycle-pedal mechanism, hula-twist mechanism) attempt to explain how the retinal group can change its conformation without clashing with the enveloping rhodopsin protein pocket.

Recent data support that it is a functional monomer- as opposed to a dimer- which was the paradigm of G-protein-coupled receptors for many years.

Phototransduction
Rhodopsin is an essential G-protein receptor in is_associated_with::phototransduction.

Function
Metarhodopsin II activates the G protein is_associated_with::transducin (Gt) to activate the is_associated_with::visual phototransduction pathway. When transducin's α subunit is bound to GTP, it activates cGMP phosphodiesterase. cGMP phosphodiesterase hydrolyzes cGMP (breaks it down). cGMP can no longer activate cation channels. This leads to the hyperpolarization of photoreceptor cells and a change in the rate of transmitter release by these photoreceptor cells.

Deactivation
Meta II is deactivated rapidly after activating transducin by rhodopsin kinase and is_associated_with::arrestin. The 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. 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.

Rhodopsin and retinal disease
Mutation of the rhodopsin gene is a major contributor to various retinopathies such as is_associated_with::retinitis pigmentosa. In general, the disease-causing protein aggregates with is_associated_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 is_associated_with::apoptosis. Other mutations on rhodopsin lead to is_associated_with::X-linked congenital stationary night blindness, mainly due to constitutive activation, when the mutations occur around the chromophore binding pocket of rhodopsin. Several other pathological states relating to rhodopsin have been discovered including poor post-Golgi trafficking, dysregulative activation, rod outer segment instability and arrestin binding.

Microbial rhodopsins
Some is_associated_with::prokaryotes express is_associated_with::proton pumps called is_associated_with::bacteriorhodopsins, is_associated_with::proteorhodopsins, and is_associated_with::xanthorhodopsins to carry out is_associated_with::phototrophy. 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 is_associated_with::halorhodopsins are light-activated chloride pumps. Unicellular flagellate algae contain is_associated_with::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. While all microbial rhodopsins have significant is_associated_with::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 is_associated_with::Structural Classification of Proteins (SCOP).