Transient receptor potential (TRP) channels are a diverse class of ion channels that serve as polymodal regulated sensors. They are widely expressed and function in diverse physiological roles in health and disease. Interest in TRP channels have emerged for therapeutic intervention for diverse indications, including pathophysiologies such as pain, cancer, and obesity. Among the TRP channel family are a subset of proteins that function as molecular thermometers sensing biological temperature, where they convert changes in thermal energy to conformational change (work), a feature that is central to thermosensing and thermoregulation. Additionally, these proteins are modulated by a variety of other stimuli including voltage, chemical ligands, lipids, pH, and modulatory proteins. On the path to understanding the molecular mechanisms of how this class of membrane proteins integrate diverse stimuli, a structural, functional, and thermodynamically integrated approach is being employed. These techniques include solution NMR, computational modeling, and electrophysiology. The data will focus on our studies of thermosensing TRP channels and the emerging view of the mechanistic interplay between regulatory modes in TRP channel structure and function.

Dissecting the polymodal gating and modulation of TRP channels

254th National Meeting (2017)

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