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Plos One : Integrative Binding Sites Within Intracellular Termini of Trpv1 Receptor, Volume 7

By Obukhov, Alexander G.

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Book Id: WPLBN0003939670
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos One : Integrative Binding Sites Within Intracellular Termini of Trpv1 Receptor, Volume 7  
Author: Obukhov, Alexander G.
Volume: Volume 7
Language: English
Subject: Journals, Science, Medical Science
Collections: Periodicals: Journal and Magazine Collection (Contemporary)
Historic
Publication Date:
Publisher: Plos

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Obukhov, A. G. (n.d.). Plos One : Integrative Binding Sites Within Intracellular Termini of Trpv1 Receptor, Volume 7. Retrieved from http://netlibrary.net/


Description
Description : TRPV1 is a nonselective cation channel that integrates wide range of painful stimuli. It has been shown that its activity could be modulated by intracellular ligands PIP2 or calmodulin (CaM). The detailed localization and description of PIP2 interaction sites remain unclear. Here, we used synthesized peptides and purified fusion proteins of intracellular regions of TRPV1 expressed in E.coli in combination with fluorescence anisotropy and surface plasmon resonance measurements to characterize the PIP2 binding to TRPV1. We characterized one PIP2 binding site in TRPV1 N-terminal region, residues F189- V221, and two independent PIP2 binding sites in C–terminus : residues K688-K718 and L777-S820. Moreover we show that two regions, namely F189-V221 and L777-S820, overlap with previously localized CaM binding sites. For all the interactions the equilibrium dissociation constants were estimated. As the structural data regarding C-terminus of TRPV1 are lacking, restraint-based molecular modeling combined with ligand docking was performed providing us with structural insight to the TRPV1/PIP2 binding. Our experimental results are in excellent agreement with our in silico predictions.

 

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