Exploring TRPC3 Interaction with Cholesterol through Coarse-Grained Molecular Dynamics Simulations.

ABSTRACT: Transient receptor potential canonical 3 (TRPC3) channel belongs to the superfamily of transient receptor potential (TRP) channels which mediate Ca²⁺ influx into the cell. These channels constitute essential elements of cellular signalling and have been implicated in a wide range of diseases. TRPC3 is primarily gated by lipids and its surface expression has been shown to be dependent on cholesterol, yet a comprehensive exploration of its interaction with this lipid has thus far not emerged. Here, through 80 µs of coarse-grained molecular dynamics simulations, we show that cholesterol interacts with multiple elements of the transmembrane machinery of TRPC3. Through our approach, we identify an annular binding site for cholesterol on the pre-S1 helix and a non-annular site at the

SUBMITTER: Clarke A 

PROVIDER: S-EPMC9313397 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature