Structural insights on TRPV5 gating by endogenous modulators.

ABSTRACT: TRPV5 is a transient receptor potential channel involved in calcium reabsorption. Here we investigate the interaction of two endogenous modulators with TRPV5. Both phosphatidylinositol 4,5-bisphosphate (PI(4,5)P₂) and calmodulin (CaM) have been shown to directly bind to TRPV5 and activate or inactivate the channel, respectively. Using cryo-electron microscopy (cryo-EM), we determined TRPV5 structures in the presence of dioctanoyl PI(4,5)P₂ and CaM. The PI(4,5)P₂ structure reveals a binding site between the N-linker, S4-S5 linker and S6 helix of TRPV5. These interactions with PI(4,5)P₂ induce conformational rearrangements in the lower gate, opening the channel. The CaM structure reveals two TRPV5 C-terminal peptides anchoring a single CaM molecule

SUBMITTER: Hughes TET 

PROVIDER: S-EPMC6179994 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature