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  Regulation of lipid saturation without sensing membrane fluidity

Ballweg, S., Sezgin, E., Doktorova, M., Covino, R., Reinhard, J., Wunnicke, D., et al. (2020). Regulation of lipid saturation without sensing membrane fluidity. Nature Communications, 11: 756. doi:10.1038/s41467-020-14528-1.

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 Creators:
Ballweg, Stephanie1, 2, Author
Sezgin, Erdinc3, Author
Doktorova, Milka4, Author
Covino, Roberto5, Author           
Reinhard, John1, 2, Author
Wunnicke, Dorith6, Author
Hänelt, Inga6, Author
Levental, Ilya4, Author
Hummer, Gerhard5, 7, Author           
Ernst, Robert1, 2, Author
Affiliations:
1Medical Biochemistry and Molecular Biology, Medical Faculty, Saarland Universit, Homburg, Germany, ou_persistent22              
2PZMS, Center for Molecular Signaling, Medical Faculty, Saarland University, Homburg, Germany, ou_persistent22              
3MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK, ou_persistent22              
4Department of Integrative Biology and Pharmacology, McGovern Medical School at the University of Texas Health Science Center, Houston, Texas, USA, ou_persistent22              
5Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society, ou_2068292              
6Institute of Biochemistry, Goethe University Frankfurt, Frankfurt, Germany, ou_persistent22              
7Institute of Biophysics, Goethe University Frankfurt, Frankfurt, Germany, ou_persistent22              

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 Abstract: Cells maintain membrane fluidity by regulating lipid saturation, but the molecular mechanisms of this homeoviscous adaptation remain poorly understood. We have reconstituted the core machinery for regulating lipid saturation in baker's yeast to study its molecular mechanism. By combining molecular dynamics simulations with experiments, we uncover a remarkable sensitivity of the transcriptional regulator Mga2 to the abundance, position, and configuration of double bonds in lipid acyl chains, and provide insights into the molecular rules of membrane adaptation. Our data challenge the prevailing hypothesis that membrane fluidity serves as the measured variable for regulating lipid saturation. Rather, we show that Mga2 senses the molecular lipid-packing density in a defined region of the membrane. Our findings suggest that membrane property sensors have evolved remarkable sensitivities to highly specific aspects of membrane structure and dynamics, thus paving the way toward the development of genetically encoded reporters for such properties in the future.

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Language(s): eng - English
 Dates: 2019-07-162020-01-142020-02-06
 Publication Status: Published online
 Pages: 13
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41467-020-14528-1
BibTex Citekey: ballweg_regulation_2020
 Degree: -

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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 11 Sequence Number: 756 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723