Lipid composition and salt concentration as regulatory factors of the anion selectivity of VDAC studied by coarse-grained molecular dynamics simulations

TitleLipid composition and salt concentration as regulatory factors of the anion selectivity of VDAC studied by coarse-grained molecular dynamics simulations
Publication TypeJournal Article
Year of Publication2019
AuthorsVan Liefferinge, F, Krammer, E-M, Sengupta, D, Prevost, M
JournalChemistry and Physics of Lipids
Volume220
Pagination66-76
Date PublishedMAY
Type of ArticleArticle
ISSN0009-3084
KeywordsCoarse-grained molecular, Membrane channel, Protein-lipid interactions, VDAC
Abstract

The voltage-dependent anion channel (VDAC) is a mitochondrial outer membrane protein whose fundamental function is to facilitate and regulate the flow of metabolites between the cytosol and the mitochondrial inter membrane space. Using coarse-grained molecular dynamics simulations, we investigated the dependence of VDAC selectivity towards small inorganic anions on two factors: the ionic strength and the lipid composition. In agreement with experimental data we found that VDAC becomes less anion selective with increasing salt concentration due to the screening of a few basic residues that point into the pore lumen. The molecular dynamics simulations provide insight into the regulation mechanism of VDAC selectivity by the composition in the lipid membrane and suggest that the ion distribution is differently modulated by POPE compared to the POPC bilayer. This occurs through the more persistent interactions of acidic residues located at both rims of the beta-barrel with head groups of POPE which in turn impact the electrostatic potential and thereby the selectivity of the pore. This mechanism occurs not only in POPE single component membranes but also in a mixed POPE/POPC bilayer by an enrichment of POPE over POPC lipids on the surface of VDAC. Thus we show here that computationally-in-expensive coarse-grained simulations are able to capture, in a semi-quantitative way, essential features of VDAC anion selectivity and could pave the way toward a molecular level understanding of metabolite transport in natural membranes.

DOI10.1016/j.chemphyslip.2018.11.002
Type of Journal (Indian or Foreign)

Foreign

Impact Factor (IF)

2.536

Divison category: 
Physical and Materials Chemistry

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