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

Faraday Discuss. 2013:161:347-63; discussion 419-59. doi: 10.1039/c2fd20086d.

Abstract

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.

MeSH terms

  • Amino Acid Sequence
  • G(M1) Ganglioside / chemistry
  • G(M1) Ganglioside / metabolism
  • Gangliosides / chemistry
  • Gangliosides / metabolism*
  • Hedgehog Proteins / chemistry
  • Hedgehog Proteins / metabolism
  • Lipid-Linked Proteins / chemistry
  • Lipid-Linked Proteins / metabolism*
  • Membrane Microdomains / chemistry*
  • Membrane Microdomains / metabolism*
  • Molecular Dynamics Simulation
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Protein Transport*
  • ras Proteins / chemistry
  • ras Proteins / metabolism*

Substances

  • Gangliosides
  • Hedgehog Proteins
  • Lipid-Linked Proteins
  • G(M1) Ganglioside
  • ras Proteins