Structural insight into TRPV5 channel function and modulation.

Dang, Shangyu; van Goor, Mark K; Asarnow, Daniel; Wang, YongQiang; Julius, David; Cheng, Yifan; van der Wijst, Jenny · Proc Natl Acad Sci U S A · 2019

basic_science · Level V

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Abstract

TRPV5 (transient receptor potential vanilloid 5) is a unique calcium-selective TRP channel essential for calcium homeostasis. Unlike other TRPV channels, TRPV5 and its close homolog, TRPV6, do not exhibit thermosensitivity or ligand-dependent activation but are constitutively open at physiological membrane potentials and modulated by calmodulin (CaM) in a calcium-dependent manner. Here we report high-resolution electron cryomicroscopy structures of truncated and full-length TRPV5 in lipid nanodiscs, as well as of a TRPV5 W583A mutant and TRPV5 in complex with CaM. These structures highlight the mechanism of calcium regulation and reveal a flexible stoichiometry of CaM binding to TRPV5.

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