Structural insight into TRPV5 channel function and modulation

Proc Natl Acad Sci U S A. 2019 Apr 30;116(18):8869-8878. doi: 10.1073/pnas.1820323116. Epub 2019 Apr 11.

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.

Keywords: TRP channel; calcium; calmodulin; cryo-EM.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Radioisotopes
  • Cloning, Molecular
  • Cryoelectron Microscopy
  • Models, Chemical
  • Models, Molecular
  • Mutation
  • Protein Binding
  • Protein Conformation
  • Rabbits
  • TRPV Cation Channels / classification
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / physiology*
  • TRPV Cation Channels / ultrastructure*

Substances

  • Calcium Radioisotopes
  • TRPV Cation Channels
  • Calcium

Associated data

  • PDB/6O1N
  • PDB/6O1P
  • PDB/6O1U
  • PDB/6O20