Thermodynamic and structural basis of temperature-dependent gating in TRP channels

Living organisms require detecting the environmental thermal clues for survival, allowing them to avoid noxious stimuli or find prey moving in the dark. In mammals, the Transient Receptor Potential ion channels superfamily is constituted by 27 polymodal receptors whose activity is controlled by small ligands, peptide toxins, protons and voltage. The thermoTRP channels subgroup exhibits unparalleled temperature dependence -behaving as heat and cold sensors. Functional studies have dissected their biophysical features in detail, and the advances of single-particle Cryogenic Electron microscopy provided the structural framework required to propose detailed channel gating mechanisms. However, merging structural and functional evidence for temperature-driven gating of thermoTRP channels has been a hard nut to crack, remaining an open question nowadays. Here we revisit the highlights on the study of heat and cold sensing in thermoTRP channels in the light of the structural data that has emerged during recent years.