PubMed 26387779

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPA , TRPA1 , TRPV , TRPV1

Title: How the TRPA1 receptor transmits painful stimuli: Inner workings revealed by electron cryomicroscopy.

Authors: Monique S J Brewster, Rachelle Gaudet

Journal, date & volume: Bioessays, 2015 Sep 21 , ,

PubMed link:

A new high-resolution structure of a pain-sensing ion channel, TRPA1, provides a molecular scaffold to understand channel function. Unexpected structural features include a TRP-domain helix similar to TRPV1, a novel ligand-binding site, and an unusual C-terminal coiled coil stabilized by inositol hexakisphosphate (IP6). TRP-domain helices, which structurally act as a nexus for communication between the channel gates and its other domains, may thus be a feature conserved across the entire TRP family and, possibly, other allosterically-gated channels. Similarly, the TRPA1 antagonist-binding site could also represent a druggable location in other ion channels. Combined with known TRPA1 functional properties, the structural role for IP6 leads us to propose that polyphosphate unbinding could act as a molecular kill switch for TRPA1 inactivation. Finally, although packing of the TRPA1 membrane-proximal region hints at a mechanism for electrophile sensing, the details of how TRPA1 responds to noxious reactive electrophiles and temperature await future studies.