RT Journal Article
SR Electronic
T1 Lipid-mediated Association of the Slg1 Transmembrane Domains in Yeast Plasma Membranes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.06.29.450341
DO 10.1101/2021.06.29.450341
A1 Alavizargar, Azadeh
A1 Elting, Annegret
A1 Wedlich-Söldner, Roland
A1 Heuer, Andreas
YR 2022
UL http://biorxiv.org/content/early/2022/01/12/2021.06.29.450341.abstract
AB Clustering of transmembrane proteins underlies a multitude of fundamental biological processes at the plasma membrane (PM) such as receptor activation, lateral domain formation and mechanotransduction. The self-association of the respective transmembrane domains (TMD) has also been suggested to be responsible for the micron-scaled patterns seen for integral membrane proteins in the budding yeast plasma membrane. However, the underlying interplay between local lipid composition and TMD identity is still not mechanistically understood. In this work we combined coarse-grained molecular dynamics (MD) simulations of simplified bilayer systems with high resolution live-cell microscopy to analyze the distribution of a representative helical yeast TMD from the PM sensor Slg1 within different lipid environments. In our simulations we specifically evaluated the effects of acyl chain saturation and anionic lipids head groups on the association of two TMDs. We found that weak lipid-protein interactions significantly affect the configuration of TMD dimers and the free energy of association. Increased amounts of unsaturated phospholipids strongly reduced helix-helix interaction, while the presence of anionic phosphatidylserine (PS) hardly affected dimer formation. We could experimentally confirm this surprising lack of effect of PS using the network factor, a mesoscopic measure of PM pattern formation in yeast cells. Simulations also showed that formation of TMD dimers in turn increased the order parameter of the surrounding lipids and induced long-range perturbations in lipid organization. In summary, our results shed new light on the mechanisms for lipid-mediated dimerization of TMDs in complex lipid mixtures.Competing Interest StatementThe authors have declared no competing interest.