Bidirectional Allosteric Coupling between PIP₂ Binding and the Pore of the Oncochannel TRPV6.

ABSTRACT: The epithelial ion channel TRPV6 plays a pivotal role in calcium homeostasis. Channel function is intricately regulated at different stages, involving the lipid phosphatidylinositol-4,5-bisphosphate (PIP₂). Given that dysregulation of TRPV6 is associated with various diseases, including different types of cancer, there is a compelling need for its pharmacological targeting. Structural studies provide insights on how TRPV6 is affected by different inhibitors, with some binding to sites else occupied by lipids. These include the small molecule cis-22a, which, however, also binds to and thereby blocks the pore. By combining calcium imaging, electrophysiology and optogenetics, we identified residues within the pore and the lipid binding site that are relevant for regulation by cis-2

SUBMITTER: Humer C 

PROVIDER: S-EPMC10779433 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature