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| | === Allosteric Effects === | | === Allosteric Effects === |
| - | | + | Sodium ions are a negative allosteric inhibitor to the binding of the neurotensin agonist to the binding site on the neurotensin receptor. |
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| - | This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
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Revision as of 04:24, 29 March 2016
Neurotensin Receptor (Rattus norvegicus)
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Introduction
The neurotensin receptor (NTSR1) belongs to the superfamily of proteins known as G protein-coupled receptors (GPCRs) and responds to the 13 amino acid hormone neurotensin (NT). There are currently around 800 G protein-coupled receptors that have been identified and are thought to be responsible for roughly 80% of signal transduction across the cell membrane.(reference year in g protein) These receptors are involved in a vast array of physiological processes within the body that range from interactions with dopamine to effects on secretion of bile in the intestines.(reference enhancement jujunem) (Reference dopamine) Due to the vast array of functions that these proteins serve and their high abundance within the body, these proteins have become a major site of drug targets in medicine making a deeper, more in depth understanding of these proteins very important. (drug discovery) There are currently no NTRS1 structures of the inactive state, so there is no way to determine the conformational changes of the binding pocket caused by the binding of NT. (reference Agonist-bound)
Neurotensin
Structure
Overall Structure
Like other G protein-coupled receptors, the neurotensin receptor is composed of 3 distinct regions. An extracellular binding site where neurotensin binds and causes a conformational change of the protein, a region containing that transduce the signal from the extracellular side of the cell membrane to the intracellular side, and an intracellular region that, when activated by a conformational change in the protein, activates a G protein associated with this receptor. There are currently no crystal structures of the inactive form of the neurotensin receptor available. Without a representation of the inactive form, the conformational changes caused by agonist binding are still not completely known.
Neurotensin Binding Site
Hydrophobic Stacking
A major player in the transduction of the extracellular signal to the intracellular G protein is the hydrogen bonding network that links the bound hormone with the hydrophobic core of the neurotensin receptor. The carboxylate of L13 forms a hydrogen bond network with R327, R328, and Y324. The Y324, in turn, is brought into an orientation to make the formation of a network between F358, W321, A157, and F317 possible.(Reference structural prereq) The conformational changes caused by this stacking allows for the signal to be moved from the extracellular binding site through the transmembrane helices of the receptor to the intracellular region activating the G protein.
Sodium Binding Pocket
Allosteric Effects
Sodium ions are a negative allosteric inhibitor to the binding of the neurotensin agonist to the binding site on the neurotensin receptor.
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References
Millar, Robert P., and Claire L. Newton. "The year in G protein-coupled receptor research." Molecular endocrinology 24.1 (2010): 261-274.
Fredriksson, Robert, et al. "The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints." Molecular pharmacology 63.6 (2003): 1256-1272.
Gui, Xianyong, and Robert E. Carraway. "Enhancement of jejunal absorption of conjugated bile acid by neurotensin in rats." Gastroenterology 120.1 (2001): 151-160.
Binder, Elisabeth B., et al. "Neurotensin and dopamine interactions."Pharmacological reviews 53.4 (2001): 453-486.
Fang, Ye, Joydeep Lahiri, and Laurent Picard. "G protein-coupled receptor microarrays for drug discovery." Drug discovery today 8.16 (2003): 755-761.
White, Jim F. et al. “Structure of the Agonist-Bound Neurotensin Receptor.” Nature 490.7421 (2012): 508–513. PMC. Web. 29 Mar. 2016.
Krumm, Brian E., et al. "Structural prerequisites for G-protein activation by the neurotensin receptor." Nature communications 6 (2015).
