Origami in the outer membrane: the transmembrane arrangement of mitochondrial porins.
Voltage-dependent anion-selective channels (VDAC), also known as mitochondrial porins, are key regulators of metabolite flow across the mitochondrial outer membrane. Porins from a wide variety of organisms share remarkably similar electrophysiological properties, in spite of considerable sequence dissimilarity, indicating that they share a common structure. Based on primary sequence considerations, analogy with bacterial porins, and circular dichroism analysis, it is agreed that VDAC spans the outer membrane as a beta-barrel. However, the residues that form the antiparallel beta-strands comprising this barrel remain unknown. Various predictive methods, largely based on the known structures of bacterial beta-barrels, have been applied to the primary sequences of VDAC. Refinement and confirmation of these predictions have developed through numerous investigations of wild-type and variant porins, both in mitochondria and in artificial membranes. These experiments have involved VDAC from several sources, precluding the generation of a unified model. Herein, using the Neurospora VDAC sequence as a template, the published structural information and predictions have been reassessed to delineate a model that satisfies most of the available data.
Bay
Denice C
DC
Department of Microbiology, University of Manitoba, Winnipeg, Canada.
Court
Deborah A
DA
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002942:Circular Dichroism; D005544:Forecasting; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000737:chemistry* / Q000502:physiology*; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology; D008928:Mitochondria / Q000502:physiology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018272:Porins / Q000737:chemistry* / Q000502:physiology*; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D050994:Voltage-Dependent Anion Channels
D007473:Ion Channels; D008565:Membrane Proteins; D018272:Porins; D050994:Voltage-Dependent Anion Channels