Journal Article

Regulation of lipid saturation without sensing membrane fluidity

Reinhard, John, Sezgin, Erdinc, Hummer, Gerhard, Covino, Roberto, Wunnicke, Dorith, Doktorova, Milka, Ernst, Robert, Levental, Ilya, Hänelt, Inga, Ballweg, Stephanie

2020

Overview

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. Cells maintain membrane fluidity by regulating lipid saturation, but the molecular mechanisms of this homeoviscous adaptation remain poorly understood. Here authors reconstituted the core machinery for regulating lipid saturation in baker’s yeast to directly characterize its response to defined membrane environments and uncover its mode-of-action.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/1 / 631/45/287/1192 / 631/57/2271 / 631/80/313/1463 / 82/16 / 82/83 / 9/10 / 96/33 / 96/34 / 96/95 / Adaptation / Amino Acid Substitution / Biosensing Techniques - methods / Fluidity / Fluorescence Resonance Energy Transfer / Genetic code / Humanities and Social Sciences / Lipids / Membrane Fluidity / Membrane Lipids - chemistry / Membrane Lipids - metabolism / Membrane Proteins - chemistry / Membrane Proteins - genetics / Membrane Proteins - metabolism / Membrane structure / Membrane structures / Membranes / Models, Biological / Molecular dynamics / Molecular Dynamics Simulation / Molecular modelling / multidisciplinary / Mutagenesis, Site-Directed / Packing density / Saccharomyces cerevisiae - genetics / Saccharomyces cerevisiae - metabolism / Saccharomyces cerevisiae Proteins - chemistry / Saccharomyces cerevisiae Proteins - genetics / Saccharomyces cerevisiae Proteins - metabolism / Saturation / Science / Science (multidisciplinary) / Sensitivity / Transcription / Transcription Factors - chemistry / Transcription Factors - genetics / Transcription Factors - metabolism / Viscosity / Yeast