Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

Title: Comparative sequence analysis suggests a conserved gating mechanism for TRP channels.

Authors: Eugene Palovcak, Lucie Delemotte, Michael L Klein, Vincenzo Carnevale

Journal, date & volume: J. Gen. Physiol., 2015 Jul , 146, 37-50

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26078053

Abstract
The transient receptor potential (TRP) channel superfamily plays a central role in transducing diverse sensory stimuli in eukaryotes. Although dissimilar in sequence and domain organization, all known TRP channels act as polymodal cellular sensors and form tetrameric assemblies similar to those of their distant relatives, the voltage-gated potassium (Kv) channels. Here, we investigated the related questions of whether the allosteric mechanism underlying polymodal gating is common to all TRP channels, and how this mechanism differs from that underpinning Kv channel voltage sensitivity. To provide insight into these questions, we performed comparative sequence analysis on large, comprehensive ensembles of TRP and Kv channel sequences, contextualizing the patterns of conservation and correlation observed in the TRP channel sequences in light of the well-studied Kv channels. We report sequence features that are specific to TRP channels and, based on insight from recent TRPV1 structures, we suggest a model of TRP channel gating that differs substantially from the one mediating voltage sensitivity in Kv channels. The common mechanism underlying polymodal gating involves the displacement of a defect in the H-bond network of S6 that changes the orientation of the pore-lining residues at the hydrophobic gate.