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J Cell Biol. 2018 Sep 3;217(9):3109-3126. doi: 10.1083/jcb.201802027. Epub 2018 Jun 25.

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

Author information

1
Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Frankfurt, Germany harald.f.hofbauer@gmail.com.
2
Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Frankfurt, Germany.
3
Institute of Medical Biochemistry and Molecular Biology, School of Medicine, University of Saarland, Homburg, Germany.
4
Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Frankfurt, Germany.
5
Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Frankfurt, Germany.
6
Physical Biology, Interdisciplinary Center for Neuroscience, Goethe University Frankfurt, Frankfurt, Germany.
7
Institute for Biophysics, Goethe University Frankfurt, Frankfurt, Germany.
8
Institute of Medical Biochemistry and Molecular Biology, School of Medicine, University of Saarland, Homburg, Germany robert.ernst@uks.eu.

Abstract

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.

PMID:
29941475
PMCID:
PMC6122994
DOI:
10.1083/jcb.201802027
[Indexed for MEDLINE]
Free PMC Article

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