Temperature-induced structural changes in thermosensitive transient receptor potential channels (thermoTRPs).

The ability to sense environmental temperature is fundamental to animal survival, physiological homeostasis, and adaptation to changing environments. Animals rely on temperature-responsive molecules to detect changes in environmental and internal temperatures to maintain their thermal homeostasis. Among these molecules, the best-characterized group belongs to the transient receptor potential (TRP) channel superfamily, commonly referred to as thermoTRPs. ThermoTRPs have been extensively studied and are well established as thermoreceptors. In recent years, cryo-electron microscopy (cryo-EM) has enabled the structural characterization of numerous thermoTRP channels in their closed-state and agonist-induced open state, providing unprecedented insights into their architecture and gating mechanisms. Despite these advances, the molecular mechanisms by which thermoTRPs undergo temperature-induced activation remain poorly understood. This review focuses on six pioneering cryo-EM studies reporting temperature-induced open structures to summarize current structural evidence and discuss potential mechanisms by which temperature drives channel opening in thermoTRPs.