Molecular View on Protein Sorting into Liquid-ordered Membrane Domains Mediated by Gangliosides and Lipid Anchors

We present results from coarse grain molecular dynamics simulations of mixed model membranes consisting of saturated and unsaturated lipids together with cholesterol, in which lipid-anchored membrane proteins are embedded. The membrane proteins studied are the peripherally bound H-Ras, N-Ras, and Hedgehog, and the transmembrane peptides WALP and LAT. We provide a molecular view on how the presence and nature of these lipid anchors affects partitioning of the proteins between liquid-ordered and liquid-disordered domains. In addition, we probed the role of the ganglioside lipid GM1 on the protein sorting, showing formation of GM1-protein nano-domains that act as shuttles between the differently ordered membrane regions.