title: Mdm10 is an ancient eukaryotic porin co-occurring with the ERMES complex.
abstract: Mitochondrial β-barrel proteins fulfill central functions in the outer membrane like metabolite exchange catalyzed by the voltage-dependent anion channel (VDAC) and protein biogenesis by the central components of the preprotein translocase of the outer membrane (Tom40) or of the sorting and assembly machinery (Sam50). The mitochondrial division and morphology protein Mdm10 is another essential outer membrane protein with proposed β-barrel fold, which has so far only been found in Fungi. Mdm10 is part of the endoplasmic reticulum mitochondria encounter structure (ERMES), which tethers the ER to mitochondria and associates with the SAM complex. In here, we provide evidence that Mdm10 phylogenetically belongs to the VDAC/Tom40 superfamily. Contrary to Tom40 and VDAC, Mdm10 exposes long loops towards both sides of the membrane. Analyses of single loop deletion mutants of Mdm10 in the yeast Saccharomyces cerevisiae reveal that the loops are dispensable for Mdm10 function. Sequences similar to fungal Mdm10 can be found in species from Excavates to Fungi, but neither in Metazoa nor in plants. Strikingly, the presence of Mdm10 coincides with the appearance of the other ERMES components. Mdm10's presence in both unikonts and bikonts indicates an introduction at an early time point in eukaryotic evolution.
authors.affiliation: JWGU Frankfurt am Main, Cluster of Excellence Macromolecular Complexes, Centre of Membrane Proteomics, Department of Biosciences, Max-von-Laue Str. 9, 60438 Frankfurt, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Flinner
authors.affiliation: Institut für Biochemie und Molekularbiologie, Universität Freiburg, D-79104 Freiburg, Germany; Fakultät für Biologie, Universität Freiburg, D-79104 Freiburg, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Ellenrieder
authors.affiliation: Institut für Biochemie und Molekularbiologie, Universität Freiburg, D-79104 Freiburg, Germany; Fakultät für Biologie, Universität Freiburg, D-79104 Freiburg, Germany.
authors.forename: Sebastian B
authors.initials: SB
authors.lastname: Stiller
authors.affiliation: Institut für Biochemie und Molekularbiologie, Universität Freiburg, D-79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Universität Freiburg, D-79104 Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
authors.affiliation: JWGU Frankfurt am Main, Cluster of Excellence Macromolecular Complexes, Centre of Membrane Proteomics, Department of Biosciences, Max-von-Laue Str. 9, 60438 Frankfurt, Germany. Electronic address: schleiff@bio.uni-frankfurt.de.
authors.forename: Enrico
authors.initials: E
authors.lastname: Schleiff
authors.affiliation: JWGU Frankfurt am Main, Cluster of Excellence Macromolecular Complexes, Centre of Membrane Proteomics, Department of Biosciences, Max-von-Laue Str. 9, 60438 Frankfurt, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Mirus
mesh_terms: D000595:Amino Acid Sequence; D016384:Consensus Sequence; D003600:Cytosol / Q000378:metabolism; D019143:Evolution, Molecular; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism*; D010802:Phylogeny; D018272:Porins / Q000737:chemistry / Q000378:metabolism*; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D017384:Sequence Deletion; D040681:Structural Homology, Protein; D050994:Voltage-Dependent Anion Channels / Q000737:chemistry / Q000378:metabolism
chemical_list: C089419:MDM10 protein, S cerevisiae; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D018272:Porins; D029701:Saccharomyces cerevisiae Proteins; D050994:Voltage-Dependent Anion Channels
keywords: ERMES; Eukaryotic β-barrel protein; Homology modeling; Multiple sequence alignment; Phylogenetic analysis; SAM