Temperature-sensitive transient receptor potential vanilloid channels: structural insights into ligand-dependent activation.

Temperature-sensitive transient receptor potential vanilloid ion channel subtypes 1-4 (thermoTRPV1-thermoTRPV4) play important roles in a wide range of physiological processes, including temperature sensing and body temperature regulation, inflammation, pain, itch, maintenance of skin, bone and hair, along with osmotic regulation. ThermoTRPV function is modulated by numerous natural product compounds, such as capsaicin, camphor and cannabinoids. Because of their physiological importance and their druggability, these channels have made attractive potential targets for drug development. Since the beginning of the cryo-electron miscroscopy (cryo-EM) "resolution revolution," a lot of progress has been made towards dissecting the activation mechanisms of thermoTRPVs and mapping the binding sites for modulatory compounds. Here, we review the thermoTRPV physiology and pharmacology and summarize the current knowledge of their mechanisms of gating and ligand binding sites. LINKED ARTICLES: This article is part of a themed issue on Structure Guided Pharmacology of Membrane Proteins (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.14/issuetoc.