2:45 p.m. - 4 p.m. Location: RL 3.204
“Rotating and Gating: Molecular Mechanism of Human TRPM2 Opening”
Transient receptor potential melastatin 2 (TRPM2) is a Ca2+-permeable, non-selective cation channel implicated in the development of many inflammatory and neurodegenerative diseases. Human TRPM2 has a C-terminal NUDH9H domain that binds ADP-ribose (ADPR), and previous studies showed that the channel is co-activated by ADPR and Ca2+. However, the molecular mechanism of human TRPM2 gating remains elusive. To address the gating mechanism of human TRPM2, we resolved the structures of full-length human TRPM2 in different states. Structures of human TRPM2 alone, in complex with ADPR, and in complex with ADPR and Ca2+elucidate the mechanism of TRPM2 gating and provide a framework for the understanding of TRPM2-associated diseases.