Sites Contributing to TRPA1 Activation by the Anesthetic Propofol Identified by Photoaffinity Labeling.

ABSTRACT: In addition to inducing anesthesia, propofol activates a key component of the pain pathway, the transient receptor potential ankyrin 1 ion channel (TRPA1). Recent mutagenesis studies suggested a potential activation site within the transmembrane domain, near the A-967079 cavity. However, mutagenesis cannot distinguish between protein-based and ligand-based mechanisms, nor can this site explain the complex modulation by propofol. Thus more direct approaches are required to reveal potentially druggable binding sites. Here we apply photoaffinity labeling using a propofol derivative, meta-azipropofol, for direct identification of binding sites in mouse TRPA1. We confirm that meta-azipropofol activates TRPA1 like the parent anesthetic, and identify two photolabeled residues (V954 and E969) in t

SUBMITTER: Woll KA 

PROVIDER: S-EPMC5700380 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature