title: Biogenesis of the mitochondrial Hsp70 chaperone.
abstract: Chaperones mediate protein folding and prevent deleterious protein aggregation in the cell. However, little is known about the biogenesis of chaperones themselves. In this study, we report on the biogenesis of the yeast mitochondrial Hsp70 (mtHsp70) chaperone, which is essential for the functionality of mitochondria. We show in vivo and in organello that mtHsp70 rapidly folds after its import into mitochondria, with its ATPase domain and peptide-binding domain (PBD) adopting their structures independently of each other. Importantly, folding of the ATPase domain but not of the PBD was severely affected in the absence of the Hsp70 escort protein, Hep1. We reconstituted the folding of mtHsp70, demonstrating that Hep1 and ATP/ADP were required and sufficient for its de novo folding. Our data show that Hep1 bound to a folding intermediate of mtHsp70. Binding of an adenine nucleotide triggered release of Hep1 and folding of the intermediate into native mtHsp70. Thus, Hep1 acts as a specialized chaperone mediating the de novo folding of an Hsp70 chaperone.
authors.affiliation: Adolf-Butenandt-Institut, Lehrstuhl für Physiologische Chemie, Ludwig-Maximilians-Universität München, 81377 München, Germany.
authors.forename: Marta
authors.initials: M
authors.lastname: Blamowska
authors.forename: Walter
authors.initials: W
authors.lastname: Neupert
authors.forename: Kai
authors.initials: K
authors.lastname: Hell
mesh_terms: D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; C578132:Hep1 protein, S cerevisiae; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins