Transition between conformational states of the TREK-1 K2P channel promoted by interaction with PIP₂.

ABSTRACT: Members of the TREK family of two-pore domain potassium channels are highly sensitive to regulation by membrane lipids, including phosphatidylinositol-4,5-bisphosphate (PIP₂). Previous studies have demonstrated that PIP₂ increases TREK-1 channel activity; however, the mechanistic understanding of the conformational transitions induced by PIP₂ remain unclear. Here, we used coarse-grained molecular dynamics and atomistic molecular dynamics simulations to model the PIP₂-binding site on both the up and down state conformations of TREK-1. We also calculated the free energy of PIP₂ binding relative to other anionic phospholipids in both conformational states using potential of mean force and free-energy-perturbation calculations. Our results

SUBMITTER: Panasawatwong A 

PROVIDER: S-EPMC9279171 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature