TY  - INPR
A1  - Hofbauer, Harald F.
A1  - Gecht, Michael
A1  - Fischer, Sabine C.
A1  - Seybert, Anja
A1  - Frangakis, Achilleas S.
A1  - Stelzer, Ernst H. K.
A1  - Covino, Roberto
A1  - Hummer, Gerhard
A1  - Ernst, Robert
T1  - The molecular recognition of phosphatidic acid by an amphipathic helix in Opi1
T2  - bioRxiv
N2  - A key event in cellular physiology is the decision between membrane biogenesis and fat storage. Phosphatidic acid (PA) is an important lipid intermediate and signaling lipid at the branch point of these pathways and constantly monitored by the transcriptional repressor Opi1 to orchestrate lipid metabolism. Here, we report on the mechanism of membrane recognition by Opi1 and identify an amphipathic helix (AH) for the selective binding to membranes containing PA over phosphatidylserine (PS). The insertion of the AH into the hydrophobic core of the membrane renders Opi1 sensitive to the lipid acyl chain composition as an important factor contributing to the regulation of membrane biogenesis. Based on these findings, we rationally designed the membrane binding properties of Opi1 to control its responsiveness in the physiological context. Using extensive molecular dynamics (MD) simulations, we identified two PA-selective three-finger grips that tightly bind the phosphate headgroup, while interacting less intimately and more transiently with PS. This work establishes lipid headgroup selectivity as a new feature in the family of AH-containing membrane property sensors.
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/72450
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-724500
IS  - 250019
ER  -