title: Assembly of the three small Tim proteins precedes docking to the mitochondrial carrier translocase.
abstract: The mitochondrial intermembrane space contains a family of small Tim proteins that function as essential chaperones for protein import. The soluble Tim9-Tim10 complex transfers hydrophobic precursor proteins through the aqueous intermembrane space to the carrier translocase of the inner membrane (TIM22 complex). Tim12, a peripheral membrane subunit of the TIM22 complex, is thought to recruit a portion of Tim9-Tim10 to the inner membrane. It is not known, however, how Tim12 is assembled. We have identified a new intermediate in the biogenesis pathway of Tim12. A soluble form of Tim12 first assembles with Tim9 and Tim10 to form a Tim12-core complex. Tim12-core then docks onto the membrane-integrated subunits of the TIM22 complex to form the holo-translocase. Thus, the function of Tim12 in linking soluble and membrane-integrated subunits of the import machinery involves a sequential assembly mechanism of the translocase through a soluble intermediate complex of the three essential small Tim proteins.
authors.affiliation: Institut für Biochemie und Molekularbiologie, Zentrum für Biochemie und Molekulare Zellforschung, Freiburg, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Gebert
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Chacinska
authors.forename: Karina
authors.initials: K
authors.lastname: Wagner
authors.forename: Bernard
authors.initials: B
authors.lastname: Guiard
authors.forename: Carla M
authors.initials: CM
authors.lastname: Koehler
authors.forename: Peter
authors.initials: P
authors.lastname: Rehling
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Pfanner
authors.forename: Nils
authors.initials: N
authors.lastname: Wiedemann
mesh_terms: D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins; D046912:Multiprotein Complexes; D011498:Protein Precursors; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; C107250:TIM10 protein, S cerevisiae; C100674:TIM12 protein, S cerevisiae; C116366:Tim9 protein, S cerevisiae; D000226:Mitochondrial ADP, ATP Translocases