Biophysical Society Thematic Meeting | Hamburg 2022

Biophysics at the Dawn of Exascale Computers

Poster Abstracts

45-POS Board 45 DISSECTING PERILIPIN 1 MEMBRANE TARGETING AND FUNCTION USING MOLECULAR DYNAMICS SIMULATIONS Jennifer Sapia 1 ; 1 University of Fribourg, Biology, Fribourg, Switzerland Perilipins are lipid droplets (LDs) associated proteins that play a vital role in fat storage. Particularly, Perilipin 1 (or PLIN1) is essential for maintaining adipocytes' homeostasis, as it is involved in the regulation of triglyceride storage and mobilization. PLIN1 is synthesized on free ribosomes, and, under basal conditions, it constitutes a protective coating of the LD surface from lipases. PLIN1 sequence contains amphipatic helices that can reversibly bind lipid monolayers. However, a molecular mechanism describing its preferential localization to LDs is not yet known. Even if the protein structure of PLIN1 has not been solved using experimental methods, a high-confidence model of some regions of PLIN1 structure has been recently proposed thanks to AlphaFold. To investigate the mechanism through which PLIN1 localizes on the surfaces of LDs, and to gain insight into its molecular function in LD formation, we performed atomistic and coarse-grain molecular dynamics simulations of high-confidence model protein regions embedded in membrane systems mimicking LDs and the endoplasmatic reticulum membrane. Our results shed light into the dynamical behavior of PLIN1 and on its mechanism of action, providing testable molecular clues on its LD-related activity.

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