title: Concentration dependent ion selectivity in VDAC: a molecular dynamics simulation study.
abstract: The voltage-dependent anion channel (VDAC) forms the major pore in the outer mitochondrial membrane. Its high conducting open state features a moderate anion selectivity. There is some evidence indicating that the electrophysiological properties of VDAC vary with the salt concentration. Using a theoretical approach the molecular basis for this concentration dependence was investigated. Molecular dynamics simulations and continuum electrostatic calculations performed on the mouse VDAC1 isoform clearly demonstrate that the distribution of fixed charges in the channel creates an electric field, which determines the anion preference of VDAC at low salt concentration. Increasing the salt concentration in the bulk results in a higher concentration of ions in the VDAC wide pore. This event induces a large electrostatic screening of the charged residues promoting a less anion selective channel. Residues that are responsible for the electrostatic pattern of the channel were identified using the molecular dynamics trajectories. Some of these residues are found to be conserved suggesting that ion permeation between different VDAC species occurs through a common mechanism. This inference is buttressed by electrophysiological experiments performed on bean VDAC32 protein akin to mouse VDAC.
authors.affiliation: Structure et Fonction des Membranes Biologiques, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Krammer
authors.forename: Fabrice
authors.initials: F
authors.lastname: Homblé
authors.forename: Martine
authors.initials: M
authors.lastname: Prévost
mesh_terms: D000465:Algorithms; D000818:Animals; D000838:Anions; D003198:Computer Simulation; D004594:Electrophysiology / Q000379:methods; D005740:Gases; D007473:Ion Channels / Q000737:chemistry; D007477:Ions / Q000737:chemistry; D008958:Models, Molecular; D015233:Models, Statistical; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D010940:Plant Proteins / Q000378:metabolism; D010944:Plants / Q000378:metabolism; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D012492:Salts / Q000737:chemistry; D055672:Static Electricity; D050995:Voltage-Dependent Anion Channel 1 / Q000737:chemistry; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism*
chemical_list: D000838:Anions; D005740:Gases; D007473:Ion Channels; D007477:Ions; D010940:Plant Proteins; D020033:Protein Isoforms; D012492:Salts; C494762:VDAC1 protein, human; D050994:Voltage-Dependent Anion Channels; D050995:Voltage-Dependent Anion Channel 1