<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="6.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Wang, Liwen</style></author><author><style face="normal" font="default" size="100%">Cvetkov, Teresa L</style></author><author><style face="normal" font="default" size="100%">Chance, Mark R</style></author><author><style face="normal" font="default" size="100%">Moiseenkova-Bell, Vera Y</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Identification of in vivo disulfide conformation of the TRPA1 ion channel.</style></title><secondary-title><style face="normal" font="default" size="100%">J Biol Chem</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2011</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2011 Dec 29</style></date></pub-dates></dates><language><style face="normal" font="default" size="100%">ENG</style></language><abstract><style face="normal" font="default" size="100%">Transient Receptor Potential Ankyrin 1 (TRPA1) is an ion channel expressed in the termini of sensory neurons and is activated in response to a broad array of noxious exogenous and endogenous thiol-reactive compounds, making it a crucial player in chemical nociception. A number of critical cysteine residues on the channel's N-terminal domain have been identified as critical for sensing these electrophilic pungent chemicals, and our recent EM structure with modeled domains predicts that these cysteines form a ligand-binding pocket, allowing for the possibility of disulfide bonding between the cysteine residues. Here we present a comprehensive mass spectrometry investigation of the in vivo disulfide bonding conformation and in vitro reactivity of 30 of the 31 cysteine residues in the TRPA1 ion channel. Four disulfide bonds were detected in the in vivo TRPA1 structure: Cys666-Cys622, C666-Cys463, Cys622-Cys609 and Cys666-Cys193. All of the cysteines detected were reactive to NMM in vitro, with varying degrees of labeling efficiency. Comparison of the ratio of the labeling efficiency in 300 μM NMM versus 2 mM NMM identified a number of cysteine residues which were outliers from the mean labeling ratio, suggesting that protein conformation changes rendered these cysteines either more or less protected from labeling in the higher NMM concentrations. These results indicate that the activation mechanism of TRPA1 may involve N-terminal conformation changes and disulfide bonding between critical cysteine residues.</style></abstract><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/22207754?dopt=Abstract</style></custom1></record></records></xml>