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

Members of the TREK family of two-pore domain potassium channels are highly sensitive to regulation by membrane lipids, including phosphatidylinositol-4,5-bisphosphate (PIP). Previous studies have demonstrated that PIP increases TREK-1 channel activity; however, the mechanistic understanding of the conformational transitions induced by PIP remain unclear. Here, we used coarse-grained molecular dynamics and atomistic molecular dynamics simulations to model the PIP-binding site on both the up and down state conformations of TREK-1.