Mesoscopic simulations of membrane-mediated protein-protein interactions

Abstract

In this work we use coarse-grained simulations to study the dynamical behavior of transmembrane and membrane-associated proteins. First, we address acylation, a chemical modification ubiquitous in eukaryotic cells. This modification (attaching an acyl chain to a protein), serves as a membrane anchor for soluble proteins. The role of acylation for transmembrane proteins is less clear. We follow up on recent experimental indications that acylations influences trafficking of transmembrane proteins. We find that acylation significantly engances the tilting of transmembrane proteins with respect to the bilayer normal. Also hydrophobic mismatch-driven clustering and partitioning behavior is altered. Our results highlight a possible mechanism of how acylation regulates trafficking of transmembrane proteins. Second, we study monotopic membrane proteins embedded in only one membrane leaflet. We inspect how they perturb the surrounding lipid bilayer in dependence on their radius and hydrophobic length. When two or more proteins are present in the bilayer, they may colocalize. The strength of the membrane-mediated attraction between proteins depends on their geometry and thus the entropic cost of the membrane perturbation they induce. We observed the formation of a multitude of higher-order structures, e.g. corss-leaflet dimerization. We propose that the cross-leaflet dimerization may play a role in intracellular signal transduction, offering an alternative to transmembrane factors.