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Biophys J. 2015 Dec 15;109(12):2467-2470. doi: 10.1016/j.bpj.2015.11.009.

Reversible Effects of Peptide Concentration and Lipid Composition on H-Ras Lipid Anchor Clustering.

Author information

1
Department of Integrative Biology and Pharmacology, Medical School, The University of Texas Health Science Center at Houston, Houston, Texas.
2
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.

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.

PMID:
26682805
PMCID:
PMC4699922
DOI:
10.1016/j.bpj.2015.11.009
[Indexed for MEDLINE]
Free PMC Article

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