Kim, SE, Patapoutian, A and Grandl, J (2013) Single Residues in the Outer Pore of TRPV1 and TRPV3 Have Temperature-Dependent Conformations. PLoS One.

Abstract

Thermosensation is mediated by ion channels that are highly temperature-sensitive. Several members of the family of transient receptor potential (TRP) ion channels are activated by cold or hot temperatures and have been shown to function as temperature sensors in vivo. The molecular mechanism of temperature-sensitivity of these ion channels is not understood. A number of domains or even single amino acids that regulate temperature-sensitivity have been identified in several TRP channels. However, it is unclear what precise conformational changes occur upon temperature activation. Here, we used the cysteine accessibility method to probe temperature-dependent conformations of single amino acids in TRP channels. We screened over 50 amino acids in the predicted outer pore domains of the heat-activated ion channels TRPV1 and TRPV3. In both ion channels we found residues that have temperature-dependent accessibilities to the extracellular solvent. The identified residues are located within the second predicted extracellular pore loop. These residues are identical or proximal to residues that were shown to be specifically required for temperature-activation, but not chemical activation. Our data precisely locate conformational changes upon temperature-activation within the outer pore domain. Collectively, this suggests that these specific residues and the second predicted pore loop in general are crucial for the temperature-activation mechanism of these heat-activated thermoTRPs. 2013 Kim et al

Item Type:	Article
Additional Information:	pubid: 199 nvp_institute: NIBR contributor_address: (Kim, Patapoutian, Grandl) Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute (TSRI), La Jolla, CA, United States (Patapoutian) Genomic Institute of the Novartis Research Foundation (GNF), San Diego, CA, United States (Grandl) Department of Neurobiology, Duke University Medical Center, Durham, NC, United States
Date Deposited:	13 Oct 2015 13:12
Last Modified:	13 Oct 2015 13:12
URI:	https://oak.novartis.com/id/eprint/22018