title: Reversible Effects of Peptide Concentration and Lipid Composition on H-Ras Lipid Anchor Clustering.
abstract: Dynamic clusters of lipid-anchored Ras proteins are important for high-fidelity signal transduction in cells. The average size of Ras nanoclusters was reported to be independent of protein expression levels, and cholesterol depletion is commonly used to test the raft-preference of nanoclusters. However, whether protein concentration and membrane domain stability affect Ras clustering in a reversible manner is not well understood. We used coarse-grained molecular dynamics simulations to examine the reversibility of the effects of peptide and cholesterol concentrations as well as a lipid domain-perturbing nanoparticle (C60) on the dynamics and stability of H-Ras lipid-anchor nanoclusters. By comparing results from these simulations with previous observations from the literature, we show that effects of peptide/cholesterol concentrations on the dynamics and stability of H-Ras peptide nanoclusters are reversible. Our results also suggest a correlation between the stabilities of lipid domains and Ras nanoclusters, which is supported by our finding that C60 penetrates into the liquid-disordered domain of the bilayer, destabilizing lipid domains and thereby the stability of the nanoclusters.
authors.affiliation: Department of Integrative Biology and Pharmacology, Medical School, The University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Xubo
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Integrative Biology and Pharmacology, Medical School, The University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Zhenlong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Integrative Biology and Pharmacology, Medical School, The University of Texas Health Science Center at Houston, Houston, Texas. Electronic address: alemayehu.g.abebe@uth.tmc.edu.
authors.forename: Alemayehu A
authors.initials: AA
authors.lastname: Gorfe
mesh_terms: D004305:Dose-Response Relationship, Drug; D008055:Lipids / Q000737:chemistry* / Q000494:pharmacology*; D056004:Molecular Dynamics Simulation; D053758:Nanoparticles / Q000737:chemistry; D010455:Peptides / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D055550:Protein Stability / Q000187:drug effects; D018631:ras Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008055:Lipids; D010455:Peptides; D018631:ras Proteins