Origami in outer membrane mimetics: correlating the first detailed images of refolded VDAC with over 20 years of biochemical data.
Mitochondrial porin forms an aqueous pore in the outer membrane, through which selective passage of small metabolites and ions occurs, thereby regulating both mitochondrial function and cellular respiration. Investigations of the structure and function of porin have been performed with whole mitochondria, membrane vesicles, artificial membranes, and in detergent solutions, resulting in numerous models of porin structure. The mechanisms by which this protein functions are undoubtedly linked to its structure, which remained elusive until 2008, with reports of 3 high-resolution structures of this voltage-dependent, anion-selective channel (VDAC). The barrel structure is relatively simple yet unique: it is arranged as 19 anti-parallel beta-strands, with beta-strands 1 and 19 aligned parallel to each other to close the barrel. The N-terminal helical component is located within the lumen of the channel, although its precise structure and location in the lumen varies. With the basic barrel structure in hand, the data obtained in attempts to model the structure and understand porin over the past 20 years can be re-evaluated. Herein, using the mammalian VDAC structures as templates, the amassed electrophysiological and biochemical information has been reassessed with respect to the functional mechanisms of VDAC activity, with a focus on voltage-dependent gating.
Summers
William A T
WA
Department of Microbiology, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
Court
Deborah A
DA
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008928:Mitochondria / Q000502:physiology; D051336:Mitochondrial Membranes / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D050994:Voltage-Dependent Anion Channels / Q000737:chemistry*
D050994:Voltage-Dependent Anion Channels