The molecular recognition of phosphatidic acid by an amphipathic helix in Opi1

• DOI: 10.1101/250019
• Publication Date: 2018-01-19T06:10:15Z
• Authors: Harald F. Hofbauer; Michael Gecht; Sabine C. Fischer; Anja Seybert; Achilleas S. Fran...; Ernst H. K. Stelzer; Roberto Covino; Gerhard Hummer; Robert Ernst
• Keywords: Membrane Lipids; Helix (gastropod)

Abstract A key event in cellular physiology is the decision between membrane biogenesis and fat storage. Phosphatidic acid (PA) an important lipid intermediate signaling at branch point of these pathways constantly monitored by transcriptional repressor Opi1 to orchestrate metabolism. Here, we report on mechanism recognition identify amphipathic helix (AH) for selective binding membranes containing PA over phosphatidylserine (PS). The insertion AH into hydrophobic core renders sensitive acyl chain composition as factor contributing regulation biogenesis. Based findings, rationally designed properties control its responsiveness physiological context. Using extensive molecular dynamics (MD) simulations, identified two PA-selective three-finger grips that tightly bind phosphate headgroup, while interacting less intimately more transiently with PS. This work establishes headgroup selectivity a new feature family AH-containing property sensors.