{"entity": "publication", "iuid": "1fb081ed5d054cc29f56c9ffbcb48912", "timestamp": "2026-08-22T06:57:04.200Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1fb081ed5d054cc29f56c9ffbcb48912.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1fb081ed5d054cc29f56c9ffbcb48912"}}, "title": "Transition between conformational states of the TREK-1 K2P channel promoted by interaction with PIP2.", "authors": [{"family": "Panasawatwong", "given": "Adisorn", "initials": "A"}, {"family": "Pipatpolkai", "given": "Tanadet", "initials": "T"}, {"family": "Tucker", "given": "Stephen J", "initials": "SJ"}], "type": "journal article", "published": "2022-06-21", "journal": {"title": "Biophys. J.", "issn": "1542-0086", "volume": "121", "issue": "12", "pages": "2380-2388", "issn-l": "0006-3495"}, "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 identify state-dependent binding of PIP2 to sites involving the proximal C-terminus, and we show that PIP2 promotes a conformational transition from a down state toward an intermediate that resembles the up state. These results are consistent with functional data for PIP2 regulation, and together provide evidence for a structural mechanism of TREK-1 channel activation by phosphoinositides.", "doi": "10.1016/j.bpj.2022.05.019", "pmid": "35596528", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9279171"}, {"db": "pii", "key": "S0006-3495(22)00412-X"}], "notes": [], "created": "2026-08-21T11:14:06.716Z", "modified": "2026-08-21T11:14:06.742Z"}