Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Session VI Abstracts

Molecular Speciation, Dynamics and Interactions of Lipid Droplets with Proteins Dariush Mohammadyani 2 , David Barenda-Ciurana 1 , Mark Christian 1 , Valerian Kagan 2 , Judith Klein-Seetharaman 1,2 . 1 University of Warwick, Coventry, Warwickshire, United Kingdom, 2 University of Pittsburgh, Pittsburgh, PA, USA. Lipid droplets (LDs) control intracellular fat storage and allow mobilization of lipids in response to metabolic demands, playing critical roles in obesity and other metabolic disorders. They are spherical particles surrounded by a phospholipid monolayer filled with triacylglycerols, cholesterol esters and free fatty acids including oxidizable polyunsaturated molecular species. They interact with a number of proteins, which are involved in LD shape, size and lipid enzymatic reactions. To date, little is known about the biophysical properties of LD and the molecular events involved in these functions are unknown. Here, we used coarse-grained molecular dynamics simulations to shed light on structure and dynamics of LD depending on lipid composition. We developed the first computational model of a lipid droplet and optimized the parameters used based on experimental findings. We then studied its interaction with CIDEA, a protein found highly overexpressed in brown adipocytes responsible for causing enlargement of LDs. Our simulations predict CIDEA’s C-terminal helix may interact with LDs, which was experimentally confirmed by biochemical means. Our model was also useful to study the effect of lipid composition on LD structure and function. It was shown experimentally using mass spectrometry that peroxidized species are present in LDs under hypoxic conditions such as observed during dyslipidemia and cancer. Both, oxidatively-truncated forms and hydroxy- derivatives of triacyl glycerides were the prevailing oxidized lipid species. Our simulations indicate that both types of oxidized species partition preferentially into the outer monolayer surface, where they can affect essential metabolic pathways and undergo conversions possibly leading to the formation of oxygenated lipid mediators.

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