Dr. Yifan Cheng
Professor of Biochemistry and Biophysics
Howard Hughes Medical Institute
University of California, San Francisco
Title: “Structure of TRP channels by single particle cryo-EM”
Abstract: TRPV5 (transient receptor potential vanilloid) is a unique calcium-selective TRP channel that is essential for calcium homeostasis. Unlike other TRPV channels, TRPV5 and its close homologue, TRPV6, do not exhibit thermosensitivity or ligand-dependent activation, but are constitutively open at physiological membrane potentials and modulated by calmodulin in a calcium-dependent manner. Here, we report high resolution electron cryo-microscopy (cryo-EM) structures of truncated and full-length TRPV5 in lipid nanodiscs, as well as that of a TRPV5 W583A mutant and TRPV5 in complex with calmodulin (CaM). These structures highlight the mechanism of calcium regulation and reveal a flexible stoichiometry of calmodulin binding to TRPV5.