title: VDAC structure, selectivity, and dynamics.
abstract: VDAC channels exist in the mitochondrial outer membrane of all eukaryotic organisms. Of the different isoforms present in one organism, it seems that one of these is the canonical VDAC whose properties and 3D structure are highly conserved. The fundamental role of these channels is to control the flux of metabolites between the cytosol and mitochondrial spaces. Based on many functional studies, the fundamental structure of the pore wall consists of one α helix and 13 β strands tilted at a 46° angle. This results in a pore with an estimated internal diameter of 2.5nm. This structure has not yet been resolved. The published 3D structure consists of 19 β strands and is different from the functional structure that forms voltage-gated channels. The selectivity of the channel is exquisite, being able to select for ATP over molecules of the same size and charge. Voltage gating involves two separate gating processes. The mechanism involves the translocation of a positively charged portion of the wall of the channel to the membrane surface resulting in a reduction in pore diameter and volume and an inversion in ion selectivity. This mechanism is consistent with experiments probing changes in selectivity, voltage gating, kinetics and energetics. Other published mechanisms are in conflict with experimental results. This article is part of a Special Issue entitled: VDAC structure, function, and regulation of mitochondrial metabolism.
authors.affiliation: Department of Biology, University of Maryland, College Park, MD 20742, USA. columbini@umd.edu
authors.forename: Marco
authors.initials: M
authors.lastname: Colombini
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D015640:Ion Channel Gating; D008954:Models, Biological; D008969:Molecular Sequence Data; D013816:Thermodynamics; D050994:Voltage-Dependent Anion Channels / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D050994:Voltage-Dependent Anion Channels