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.
journal_name
Mol Celljournal_title
Molecular cellauthors
Covino R,Ballweg S,Stordeur C,Michaelis JB,Puth K,Wernig F,Bahrami A,Ernst AM,Hummer G,Ernst Rdoi
10.1016/j.molcel.2016.05.015subject
Has Abstractpub_date
2016-07-07 00:00:00pages
49-59issue
1eissn
1097-2765issn
1097-4164pii
S1097-2765(16)30178-2journal_volume
63pub_type
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