title: Structure and function of Hsp78, the mitochondrial ClpB homolog.
abstract: The cellular role of Hsp100/Clp chaperones in maintaining protein stability is based on two functional aspects. Under normal growth conditions they represent components of cellular protein quality control machineries that selectively remove damaged or misfolded polypeptides in cooperation with specific proteases. After thermal stress, proteins of the ClpB subfamily have the unique ability to directly resolubilize aggregated polypeptides in concert with Hsp70-type chaperones, leading to the recovery of enzymatic activity. Hsp78, the homolog of the bacterial chaperone ClpB in mitochondria of eukaryotic organisms, participates in both protective activities. Hsp78 is involved in conferring thermotolerance to the mitochondrial compartment but also participates in protein degradation by the matrix protease Pim1. Despite the high sequence conservation between Hsp78 and ClpB, an analysis of the structural properties revealed significant differences. The identified mitochondrial Hsp78s do not contain N-terminal substrate-binding domains. In addition, formation of the oligomeric chaperone complex was more variable as anticipated from the studies with bacterial ClpB. Hsp78 predominantly formed a trimeric complex under in vivo conditions. Hence, mitochondrial Hsp78s form a distinct subgroup of the ClpB chaperone family, exhibiting specific structural and functional properties.
authors.affiliation: Institut für Biochemie und Molekularbiologie, Universität Freiburg, D-79104 Freiburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Leidhold
authors.forename: Birgit
authors.initials: B
authors.lastname: von Janowsky
authors.forename: Dorothea
authors.initials: D
authors.lastname: Becker
authors.forename: Tom
authors.initials: T
authors.lastname: Bender
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Voos
mesh_terms: D000595:Amino Acid Sequence; D049071:Endopeptidase Clp / Q000737:chemistry* / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000502:physiology; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
chemical_list: D018840:HSP70 Heat-Shock Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; D049071:Endopeptidase Clp