title: A presequence- and voltage-sensitive channel of the mitochondrial preprotein translocase formed by Tim23.
abstract: Proteins imported into the mitochondrial matrix are synthesized in the cytosol with an N-terminal presequence and are translocated through hetero-oligomeric translocase complexes of the outer and inner mitochondrial membranes. The channel across the inner membrane is formed by the presequence translocase, which consists of roughly six distinct subunits; however, it is not known which subunits actually form the channel. Here we report that purified Tim23 forms a hydrophilic, approximately 13-24 A wide channel characteristic of the mitochondrial presequence translocase. The Tim23 channel is cation selective and activated by a membrane potential and presequences. The channel is formed by the C-terminal domain of Tim23 alone, whereas the N-terminal domain is required for selectivity and a high-affinity presequence interaction. Thus, Tim23 forms a voltage-sensitive high-conductance channel with specificity for mitochondrial presequences.
authors.affiliation: Institut für Biochemie und Molekularbiologie, Universität Freiburg, Hermann-Herder-Strasse 7, D-79104 Freiburg, Germany.
authors.forename: K N
authors.initials: KN
authors.lastname: Truscott
authors.forename: P
authors.initials: P
authors.lastname: Kovermann
authors.forename: A
authors.initials: A
authors.lastname: Geissler
authors.forename: A
authors.initials: A
authors.lastname: Merlin
authors.forename: M
authors.initials: M
authors.lastname: Meijer
authors.forename: A J
authors.initials: AJ
authors.lastname: Driessen
authors.forename: J
authors.initials: J
authors.lastname: Rassow
authors.forename: N
authors.initials: N
authors.lastname: Pfanner
authors.forename: R
authors.initials: R
authors.lastname: Wagner
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D004594:Electrophysiology; D007425:Intracellular Membranes / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D015640:Ion Channel Gating; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D046911:Macromolecular Substances; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000737:chemistry* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D009154:Mutation / Q000235:genetics; D010539:Permeability; D011485:Protein Binding; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000502:physiology*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D021381:Protein Transport; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D002352:Carrier Proteins; D008051:Lipid Bilayers; D008081:Liposomes; D046911:Macromolecular Substances; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D011498:Protein Precursors; D021382:Protein Sorting Signals; D021122:Protein Subunits; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C091191:TIM17 protein, S cerevisiae; C083081:TIM23 protein, S cerevisiae; C077016:TIM44 protein, S cerevisiae