Sandbox 173: Difference between revisions

==Structure==

===Rhodopsin Architecture===  

Rhodopsin consists of seven mostly α-helical transmembrane domains (H1-H7) linked sequentially by extracellular and cytoplasmic loops (E1-E3 and C1-C3 respectively), with the extracellular amino-terminal tail and the cytoplasmic carboxyl-terminal tail<ref>Article 12</ref>. Four of the helices are tilted and three of the helices are approximately perpendicular to the membrane plane<ref>Article 4</ref>. There is notable interaction between the four extracellular domains, but only a few associations are observed with the cytoplasmic domains<ref>Article 9</ref>. Helix 7 is close to being elongated around the Lysine 296 retinal attachment site, and also contains the residues Proline 291 and Proline 303, with Proline 303 being part of a conserved motif<ref>Article 9</ref>. Near the retinal region, there is a <scene name='Sandbox_173/Beta_4_strand_and_retinal/2'>β4 strand (Serine 186-Cysteine 187-Glycine 188-Isoleucine 189)</scene> within the Extracellular Helix 2 that runs almost parallel to the chromophore held in place, and is stabilized by the essential conserved  

<scene name='Sandbox_173/Disulfide_bond/4'>disulfide bond between Cysteine 110 and Cysteine 187</scene>. This loop also potentially contacts the chromophore through Glutamine 181 and Tyrosine 191<ref>Article 12</ref>.  

The structure of rhodopsin may provide stability to the important Schiff base linkage with the retinal by affecting its hydrolysis, limiting its interactions with solvent, inhibiting its release when hydrolyzed, thus encouraging rebinding of the Schiff base linkage<ref>Article 3</ref>.

===Retinal Chromophore of Rhodospin===

==Function==

===Visual Signal Transduction===

====Photoisomeration of 11-''cis'' Retinal====

The 11-''cis'' retinal (retinylidene) Schiff base functions as an inverse agonist and is prominently involved in the activation of rhodopsin. The primary step in rhodopsin photoactivation occurs in the photoisomeration of rhodopsin, as light energy absorbed from a photon is converted into chemical energy, As a photon is absorbed by the retina, the 11-cis retinylidene ligand is switched into an all-trans retinal configuration<ref>Article 2</ref>. In this extremely efficient <200 fs process, the protein-binding pocket, initially fitted to accommodate the 11-cis conformation of the chromophore, is preserved, which restrains the relaxation of the chromophore. The strained relaxation of conformational energy changes the protein state into the active form<ref>Article 2</ref>.

====Signalling Cascade and Polarization of the Cell Membrane====

The excited rhodopsin interacts with a large number of transducin molecules, found in the cytoplasic face of the disk membrane. Transducin is a member of the heterotrimeric GTP-binding proteins family, and it binds to GDP in the dark. This interaction generates a signaling cascade where transducin molecules are activated through the trigger of GDP-GTP nucleotide exchange in the α subunit<ref>Article 6</ref>.  Each activated transducin dissociates into Tα-GTP and Tβγ subunits, and Tα-GTP activates cGMP-specific phosphodiesterase by binding and removing its inhibitory subunit<ref>Textbook</ref>.  

The cGMP phosphodiesterase is an integral protein of the retina with its active site on the cytoplasmic side of the disk. Its inhibitory subunit tightly binds to it in the dark and suppresses its activity.  The now activated phosphodiesterase degrades many molecules of cGMP, efficiently decreasing the concentration of cGMP <ref>Textbook</ref>. This results in the closing of the cGMP-gated cation channels in the plasma membrane of the outer segment. The cell hyperpolarizes due to the decrease in the influx of sodium and calcium ions, results in the decrease in the release of glutamate into the synaptic cleft. This electric signal is sent to the brain through ranks of interconnecting neurons and then through the optic nerve of this hyperpolarization<ref>Article 6</ref>.

==Opsin==

===Topology Overview===

The overall dimeric structure of opsin is similar to rhodopsin, with seven transmembrane helices linked by three extracellular loops and three cytoplasmic loops and a cytoplasmic Helix 8. The small differences between the topology of the two proteins include a short helical turn in the cytoplasmic loop 1 in opsin, 1.5-2.5 helical turns longer in Helix 5 for opsin in comparison to rhodopsin, and a large outward tilt of Helix 6 of opsin<ref>Article Opsin 2</ref>. Also, in constrast to rhodopsin, opsin has two openings of the retinal-binding pocket; one of the openings is between Helix 1 and Helix 7, and the other opening is between the extracellular ends of Helix 5 and 6. This opening is formed by the residues <scene name='Sandbox_173/Opsin_retinal_opening/1'>Isoleucine 205 and Phenylalanine 208 in Helix 5, and by the residues Phenylalanine 273 and Phenylalanine 276 in Helix 6</scene><ref>Article Opsin 2</ref>. The two openings suggest different sites of retinal entrance and exit in retinal channeling<ref>Article Opsin 2</ref>.

Opsins are also photoreceptor proteins and are concentrated in cone cells, cells that are less sensitive to light but can discriminate colours, unlike rod cells. Opsins are slightly different light receptors than rhodopsin in that they can detect light from different spectrums and distinguish between their wavelengths. They have similar size, amino acid sequence, structure and transduction mechanisms as rhodopsin though. The ability to differentiate between colours is related to the three types of cone cells, each using one of the three related opsin photoreceptors<ref>Textbook</ref>.

† PDB structure used in this section: [[3cap]]