Nathalie Reuter
Affiliation
Department of Chemistry and Computational Biology Unit, University of Bergen, Norway
Allosteric control of lipid transfer proteins by membrane lipids
Abstract
Lipid transfer proteins (LTPs) transfer lipids between intracellular membranes through non-vesicular mechanisms and regulate lipid homeostasis. Despite a wealth of structural data, little is known about the mechanisms by which LTPs desorb lipids from well-organized membranes. We investigated 3 LTPs from the family of StAR-related lipid transfer domains (STARD): STARD2 (phosphatidylcholine transfer domain), STARD4 (sterol transfer domain), and STARD11 (ceramide transfer domain in CERT multidomain protein). We used a combination of multiscale molecular simulations and free energy calculations to investigate the mechanisms for extraction (or release) of their cargo lipids from (or into) their donor (or acceptor) membranes. We used multicomponent lipid bilayers modeling the plasma membrane and relevant organelle membranes. The simulations revealed similarities in binding orientation of the three proteins to lipid bilayers, but also striking differences in their sensitivity to lipid composition. We propose detailed models for the mechanism of lipid uptake/release in START domains, and highlight mechanistic differences between structurally similar proteins [1-4]. Our models are supported by experimental data.
References
[1] Talandasthi, J Mol Biol, 2024; [2] Talandasthi, J Phys Chem Lett, 2024; [3] Moqadam, J Phys Chem B, 2024, [4] Titeca, Nature, 2026