Physiology and Biophysics

December 19, 2017

PBIO seminar series: Juan Du

January 16, 2020 @ 9:30 am – 10:30 am

Ligand Recognition and Gating Mechanism of Temperature-sensitive TRPM2 channel

Juan Du, Ph.D. Assistant Professor Department of Structural Biology, Van Andel Institute Abstract:

Body temperature is one of the most critical parameters indicating human health status. It is vital for mammals to detect the ambient temperature and to have the ability to regulate the internal temperature within a narrow range to prevent tissue damage. As hypo- or hyperthermia are associated with pathological conditions such as infection, inflammation, and cancer, body temperature is a primary parameter that is monitored in patients. The body temperature is precisely regulated by the hypothalamus, which serves as the principal thermostat that coordinates body temperature by employing a number of thermosensitive ion channel receptors. These ion channels mainly belong to the TRP (transient receptor potential) superfamily. My laboratory is broadly interested in how the human body detects and responds to environmental temperature via ion channel receptors and how the temperature is regulated to prevent tissue damage. In this talk, I will talk about our structural and functional studies of a warmth-activated TRP channel, TRPM2, using single-particle cryo-EM and patch-clamp electrophysiology. We defined a novel drug binding site in TRPM2 and our results revealed a ligand-driven activation and inhibition mechanism of TRPM2. This paves a solid foundation for our long-term goal – understanding of mechanism underlying temperature-induced activation of thermosensitive ion channels.

  host: Sharona Gordon