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Mol Cell. 2016 Jul 7;63(1):49-59. doi: 10.1016/j.molcel.2016.05.015. Epub 2016 Jun 16.

A Eukaryotic Sensor for Membrane Lipid Saturation.

Author information

1
Department of Theoretical Biophysics, Max-Planck-Institute of Biophysics, 60438 Frankfurt, Germany.
2
Institute of Biochemistry and Buchmann and Institute for Molecular Life Sciences, Goethe University Frankfurt, I 60438 Frankfurt, Germany.
3
Department of Cell Biology, School of Medicine, Yale University, New Haven, CT 06510, USA.
4
Institute of Biochemistry and Buchmann and Institute for Molecular Life Sciences, Goethe University Frankfurt, I 60438 Frankfurt, Germany. Electronic address: ernst@em.uni-frankfurt.de.

Abstract

Maintaining a fluid bilayer is essential for cell signaling and survival. Lipid saturation is a key factor determining lipid packing and membrane fluidity, and it must be tightly controlled to guarantee organelle function and identity. A dedicated eukaryotic mechanism of lipid saturation sensing, however, remains elusive. Here we show that Mga2, a transcription factor conserved among fungi, acts as a lipid-packing sensor in the ER membrane to control the production of unsaturated fatty acids. Systematic mutagenesis, molecular dynamics simulations, and electron paramagnetic resonance spectroscopy identify a pivotal role of the oligomeric transmembrane helix (TMH) of Mga2 for intra-membrane sensing, and they show that the lipid environment controls the proteolytic activation of Mga2 by stabilizing alternative rotational orientations of the TMH region. This work establishes a eukaryotic strategy of lipid saturation sensing that differs significantly from the analogous bacterial mechanism relying on hydrophobic thickness.

PMID:
27320200
DOI:
10.1016/j.molcel.2016.05.015
[Indexed for MEDLINE]
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