Molecular view on protein sorting into liquid-ordered membrane domains mediated by gangliosides and lipid anchors

• DOI: 10.1039/c2fd20086d
• Publication Date: 2012-06-11T14:31:16Z
• Authors: Djurre H. de Jong; Cesar A. Lopez; Siewert J. Marrink
• Keywords: 0301 basic medicine; SONIC HEDGEHOG; Molecular Sequence Data; ASSOCIATION; G(M1) Ganglioside; MODEL MEMBRANES; Molecular Dynamics Simulation; H-RAS; Protein Structure, Tertiary; HYDROPHOBIC MISMATCH; Protein Transport; 03 medical and health sciences; Membrane Microdomains; TRANSMEMBRANE PEPTIDES; Gangliosides; FORCE-FIELD; ras Proteins; CRYSTAL-STRUCTURE; Hedgehog Proteins; Amino Acid Sequence; GROWTH-FACTOR RECEPTOR; RAFTS; Lipid-Linked Proteins

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.