TRPV Channel Structures in Health and Disease

My lab is broadly interested in the mechanisms of signaling and transport across cellular membranes. Much of our research centers on TRP channels and their role in sensory perception. We focus on temperature‐sensitive ion channels, particularly TRPV1, TRPV4 and TRPA1. TRP channels are challenging structural biology targets because they are large multidomain eukaryotic membrane proteins and are not naturally abundant. We take complementary approaches to obtain structural and functional information on TRP channels, including crystallography, biochemistry and cell‐based functional assays. The combined results advance our understanding of TRP channel function. TRPV channels play key roles in pain, thermo‐ and mechanosensation, and calcium homeostasis, and mutations in the TRPV4 channel have been implicated in both neuronal degeneration diseases and skeletal dysplasias. The N‐terminus of TRPV channels contains six ankyrin repeats, short sequence motifs often involved in protein‐ligand interactions. The isolated ARDs do not oligomerize, suggesting that they interact with regulatory factors instead. Our accumulated data provide information about how regulatory ligands interact with the ARD and other N‐ and C‐terminal intracellular regions and alter the sensitivity of these TRPV channels.