TY  - JOUR
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  - Journal of Cell Biology
N2  - A key event in cellular physiology is the decision between membrane biogenesis and fat storage. Phosphatidic acid (PA) is an important intermediate at the branch point of these pathways and is continuously monitored by the transcriptional repressor Opi1 to orchestrate lipid metabolism. In this study, we report on the mechanism of membrane recognition by Opi1 and identify an amphipathic helix (AH) for selective binding of PA over phosphatidylserine (PS). The insertion of the AH into the membrane core renders Opi1 sensitive to the lipid acyl chain composition and provides a means to adjust membrane biogenesis. By rational design of the AH, we tune the membrane-binding properties of Opi1 and control its responsiveness in vivo. Using extensive molecular dynamics simulations, we identify two PA-selective three-finger grips that tightly bind the PA phosphate headgroup while interacting less intimately 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/73686
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-736864
SN  - 0021-9525
VL  - 217
IS  - 9
SP  - 3109
EP  - 3126
PB  - Rockefeller University Press
CY  - New York, NY
ER  -