Making Sense Of Trp Channel Structures

Transient receptor potential (TRP) channels conduct cations and are typically expressed at the plasma membrane, where they act as sensors to play a role in a wide variety of biological processes. TRP channels share a common transmembrane domain containing the cation-conducting pore, and channels from different subfamilies sometimes share ligand sensitivity, ion selectivity, and temperature dependence. Despite these similarities, point mutations and small differences between closely-related channels can dramatically alter channel function. Many TRP channels lack known specific agonists or antagonists, making it difficult to study their biophysical properties and limiting our understanding of their biological functions. Near-atomic resolution structures of many TRP channels have been obtained following recent advances in the field of cryo-Electron Microscopy. While some comparisons among structures have been made, systematic quantitative analysis of all structures has been lacking. To perform a comprehensive analysis of all TRP channel structures, we aligned the conserved transmembrane domains, created a structure-based multiple sequence alignment, and analyzed global protein fold similarity, pore size, and ligand binding pockets. Leveraging the wealth of structural information provides insight into commonalities and differences among TRP channels and generates testable hypotheses for future functional studies.