title: The presequence translocase-associated protein import motor of mitochondria. Pam16 functions in an antagonistic manner to Pam18.
abstract: Transport of preproteins into the mitochondrial matrix requires the presequence translocase of the inner membrane (TIM23 complex) and the presequence translocase-associated motor (PAM). The motor consists of five essential subunits, the mitochondrial heat shock protein 70 (mtHsp70) and four cochaperones, the nucleotide exchange-factor Mge1, the translocase-associated fulcrum Tim44, the J-protein Pam18, and Pam16. Pam16 forms a complex with Pam18 and displays similarity to J-proteins but lacks the canonical tripeptide motif His-Pro-Asp (HPD). We report that Pam16 does not function as a typical J-domain protein but, rather, antagonizes the function of Pam18. Pam16 specifically inhibits the Pam18-mediated stimulation of the ATPase activity of mtHsp70. The inclusion of the HPD motif in Pam16 does not confer the ability to stimulate mtHsp70 activity. Pam16-HPD fully substitutes for wild-type Pam16 in vitro and in vivo but is not able to replace Pam18. Pam16 represents a new type of cochaperone that controls the stimulatory effect of the J-protein Pam18 and regulates the interaction of mtHsp70 with precursor proteins during import into mitochondria.
authors.affiliation: Institut für Biochemie und Molekularbiologie, Universität Freiburg, D-79104 Freiburg, Germany.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Li
authors.forename: Jan
authors.initials: J
authors.lastname: Dudek
authors.forename: Bernard
authors.initials: B
authors.lastname: Guiard
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Pfanner
authors.forename: Peter
authors.initials: P
authors.lastname: Rehling
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Voos
mesh_terms: D001483:Base Sequence; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D008969:Molecular Sequence Data; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C480348:PAM18 J protein, S cerevisiae; C484526:Pam16 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins