Structural basis of TRPV5 channel inhibition by econazole revealed by cryo-EM.

ABSTRACT: The transient receptor potential vanilloid 5 (TRPV5) channel is a member of the transient receptor potential (TRP) channel family, which is highly selective for Ca²⁺, that is present primarily at the apical membrane of distal tubule epithelial cells in the kidney and plays a key role in Ca²⁺ reabsorption. Here we present the structure of the full-length rabbit TRPV5 channel as determined using cryo-EM in complex with its inhibitor econazole. This structure reveals that econazole resides in a hydrophobic pocket analogous to that occupied by phosphatidylinositides and vanilloids in TRPV1, thus suggesting conserved mechanisms for ligand recognition and lipid binding among TRPV channels. The econazole-bound TRPV5 structure adopts a closed conformation with a distinct lowe

SUBMITTER: Hughes TET 

PROVIDER: S-EPMC5951624 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature