Sandbox 173

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Rhodopsin, a dimeric protein, is a highly characterized G protein-coupled receptor found in the neurons of the retina and in rod photoreceptor cells. It is part of the Class A (Family 1) of G protein-coupled receptors, a superfamily of membrane receptors with seven transmembrane helices<ref>Article 6</ref>. G protein-coupled receptors mediate responses to visual, olfactory, hormonal, and neurotransmitter signals among others<ref>Article 1</ref>.
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Rhodopsin, a dimeric protein, is a highly characterized G protein-coupled receptor found in the neurons of the retina and in rod photoreceptor cells. It is part of the Class A (Family 1) of G protein-coupled receptors, a superfamily of membrane receptors with seven transmembrane helices<ref>Article 6</ref>. G protein-coupled receptors mediate responses to visual, olfactory, hormonal, and neurotransmitter signals among others<ref>Article 1</ref>. Rhodopsin is known as the visual pigment, comprising of an opsin apoprotein and an 11-''cis'' retinal chromophore linked to Lysine 296 by a protonated Schiff base<ref>Article 12</ref>.
{{STRUCTURE_1u19| PDB=1u19 | SCENE= }}
{{STRUCTURE_1u19| PDB=1u19 | SCENE= }}
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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>.
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>.
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Also, there is the presence of a cationic amphipathic Helix 8, known as the fourth cytoplasmic loop, that is formed from the C-terminal tail anchoring to the membrane by two cysteines, which include palmitates in the structure. This helix runs approximately parallel to the cytoplasmic surface and is involved in Gtγ binding<ref>Article 9</ref>, as well as the modulation of rhodopsin-transducin interactions and rhodopsin-phospholipid interactions<ref>Article 12</ref>.
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Also, there is the presence of a cationic amphipathic Helix 8, known as the fourth cytoplasmic loop, that is formed from the C-terminal tail anchoring to the membrane by two cysteines, which include palmitates in the structure. This helix runs approximately parallel to the cytoplasmic surface and is involved in Gtγ binding<ref>Article 9</ref>, as well as the modulation of rhodopsin-transducin interactions and rhodopsin-phospholipid interactions<ref>Article 12</ref>.
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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 β4 strand within the Extracellular Helix 2 that runs almost parallel to the chromophore held in place, and is stabilized by the essential conserved disulfide bond between Cysteine 110 and Cysteine 187<ref>Article 12</ref>. A metal zinc ion bridge chelated by histidine side-chains and connected to the cytoplasmic ends of Helix 3 and 6 is observed to prevent receptor activation. This perhaps indicates that separation of these cytoplasmic ends would contribute to rhodopsin activation<ref>Article 10</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, and inhibiting its release when hydrolyzed, thus encouraging rebinding of the Schiff base linkage<ref>Article 3</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, and inhibiting its release when hydrolyzed, thus encouraging rebinding of the Schiff base linkage<ref>Article 3</ref>.
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===Retinal Chromophore of Rhodospin===
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Rhodopsin is bound covalently to the 11-''cis'' retinal, the chromophore or "ligand," and this retinal is found in deeply in the core of the helices, in a hydrophobic site, parallel to the lipid bilayer<ref>Article 19</ref>. This covalent binding nature is unlike most G protein-coupled receptors<ref>Article 10</ref>. The retinal is attached in the active site of rhodopsin through a protonated Schiff base bond to the ε-amino group of Lysine 296 residue on the C-terminal Helix 7, with this linkage creating a positive charge on the chromophore <ref>Article 4</ref>. As this ligand is bound in the 12-s-trans conformation, there arises the non-bonding interactions between the C-13 methyl group and C-10 hydrogen that contribute to non-planarity. This leads to the ability of the chromophore polyene tail to undergo fast photoisomerization around the C-11=C-12 double bond during light-induced activation<ref>Article 2</ref>. Somewhat enclosing this chromophore is a retinal binding pocket partially formed by the N-terminal domain overlaying the extracellular turns including Extracellular Helix 2, which folds into the molecular center<ref>Article 6</ref>.
==Function==
==Function==

Revision as of 04:11, 26 March 2010

Rhodopsin, a dimeric protein, is a highly characterized G protein-coupled receptor found in the neurons of the retina and in rod photoreceptor cells. It is part of the Class A (Family 1) of G protein-coupled receptors, a superfamily of membrane receptors with seven transmembrane helices[1]. G protein-coupled receptors mediate responses to visual, olfactory, hormonal, and neurotransmitter signals among others[2]. Rhodopsin is known as the visual pigment, comprising of an opsin apoprotein and an 11-cis retinal chromophore linked to Lysine 296 by a protonated Schiff base[3].

PDB ID 1u19

Drag the structure with the mouse to rotate
1u19, resolution 2.20Å ()
Ligands: , , , , , , , ,
Non-Standard Residues:
Related: 1f88, 1hzx, 1l9h
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Contents

Structure

Characteristic G Protein-Coupled Receptor 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[4]. Four of the helices are tilted and three of the helices are approximately perpendicular to the membrane plane[5]. There is notable interaction between the four extracellular domains, but only a few associations are observed with the cytoplasmic domains[6].

Also, there is the presence of a cationic amphipathic Helix 8, known as the fourth cytoplasmic loop, that is formed from the C-terminal tail anchoring to the membrane by two cysteines, which include palmitates in the structure. This helix runs approximately parallel to the cytoplasmic surface and is involved in Gtγ binding[7], as well as the modulation of rhodopsin-transducin interactions and rhodopsin-phospholipid interactions[8].

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[9]. Near the retinal region, there is a β4 strand within the Extracellular Helix 2 that runs almost parallel to the chromophore held in place, and is stabilized by the essential conserved disulfide bond between Cysteine 110 and Cysteine 187[10]. A metal zinc ion bridge chelated by histidine side-chains and connected to the cytoplasmic ends of Helix 3 and 6 is observed to prevent receptor activation. This perhaps indicates that separation of these cytoplasmic ends would contribute to rhodopsin activation[11].

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, and inhibiting its release when hydrolyzed, thus encouraging rebinding of the Schiff base linkage[12].

Retinal Chromophore of Rhodospin

Rhodopsin is bound covalently to the 11-cis retinal, the chromophore or "ligand," and this retinal is found in deeply in the core of the helices, in a hydrophobic site, parallel to the lipid bilayer[13]. This covalent binding nature is unlike most G protein-coupled receptors[14]. The retinal is attached in the active site of rhodopsin through a protonated Schiff base bond to the ε-amino group of Lysine 296 residue on the C-terminal Helix 7, with this linkage creating a positive charge on the chromophore [15]. As this ligand is bound in the 12-s-trans conformation, there arises the non-bonding interactions between the C-13 methyl group and C-10 hydrogen that contribute to non-planarity. This leads to the ability of the chromophore polyene tail to undergo fast photoisomerization around the C-11=C-12 double bond during light-induced activation[16]. Somewhat enclosing this chromophore is a retinal binding pocket partially formed by the N-terminal domain overlaying the extracellular turns including Extracellular Helix 2, which folds into the molecular center[17].

Function

Light-Induced Visual Signal Transduction

Light absorption and G protein activation

Opsin

References

  • Okada T, Sugihara M, Bondar AN, Elstner M, Entel P, Buss V. The retinal conformation and its environment in rhodopsin in light of a new 2.2 A crystal structure. J Mol Biol. 2004 Sep 10;342(2):571-83. PMID:15327956 doi:10.1016/j.jmb.2004.07.044
  1. ↑ Article 6
  2. ↑ Article 1
  3. ↑ Article 12
  4. ↑ Article 12
  5. ↑ Article 4
  6. ↑ Article 9
  7. ↑ Article 9
  8. ↑ Article 12
  9. ↑ Article 9
  10. ↑ Article 12
  11. ↑ Article 10
  12. ↑ Article 3
  13. ↑ Article 19
  14. ↑ Article 10
  15. ↑ Article 4
  16. ↑ Article 2
  17. ↑ Article 6
Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. Andrea Gorrell.
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