The physiological properties of a novel family of VDAC-like proteins from Drosophila melanogaster.
VDAC, a major protein of the mitochondrial outer membrane, forms voltage-dependent, anion-selective channels permeable to most metabolites. Although multiple isoforms of VDAC have been found in different organisms, only one isoform (porin/DVDAC) has been previously reported for Drosophila melanogaster. We have examined the physiological properties of three other Drosophila proteins (CG17137, CG17139, and CG17140) whose primary sequences have significant homology to DVDAC. A comparison of their hydropathy profiles (beta-pattern) with known VDAC sequences indicates the same fundamental folding pattern but with major insertions and deletions. The ability of these proteins to form channels was tested on planar membranes and liposomes. Channel activity was observed with varying degrees of similarity to VDAC. Two of these proteins (CG17137 and CG17140) produced channels with anionic selectivity in the open state. Sometimes channels exhibited closure and voltage gating, but for CG17140 this occurred at much higher voltages than is typical for VDAC. CG17139 was not able to form channels. DVDAC and CG17137 were able to rescue the temperature-sensitive conditional-lethal phenotype of VDAC-deficient yeast, whereas CG17139 and CG17140 demonstrated no complementation. Similar structure and channel formation indicate that VDAC-like proteins are part of the larger VDAC family but the modifications are indicative of specialized functions.
Komarov
Alexander G
AG
Department of Biology, University of Maryland, College Park, Maryland 20742, USA.
Graham
Brett H
BH
Craigen
William J
WJ
Colombini
Marco
M
D000595:Amino Acid Sequence; D002463:Cell Membrane Permeability / Q000502:physiology; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D018272:Porins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000145:classification / Q000378:metabolism; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D050994:Voltage-Dependent Anion Channels
D029721:Drosophila Proteins; D008081:Liposomes; D018272:Porins; D020033:Protein Isoforms; D050994:Voltage-Dependent Anion Channels; C494761:porin protein, Drosophila