title: Hsp104 and ClpB: protein disaggregating machines.
abstract: Heat-shock protein 104 (Hsp104) and caseinolytic peptidase B (ClpB), members of the AAA+ superfamily, are molecular machines involved in disaggregating insoluble protein aggregates, a process not long ago thought to be impossible. During extreme stress they are essential for cell survival. In addition, Hsp104 regulates prion assembly and disassembly. For most of their protein remodeling activities Hsp104 and ClpB work in collaboration with the Hsp70 or DnaK chaperone systems. Together, the two chaperones catalyze protein disaggregation and reactivation by a mechanism probably involving the extraction of polypeptides from aggregates by forced unfolding and translocation through the Hsp104/ClpB central cavity. The polypeptides are then released back into the cellular milieu for spontaneous or chaperone-mediated refolding.
authors.affiliation: Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Doyle
authors.forename: Sue
authors.initials: S
authors.lastname: Wickner
mesh_terms: D020816:Amino Acid Motifs; D001671:Biochemistry / Q000379:methods; D049071:Endopeptidase Clp; D029968:Escherichia coli Proteins / Q000737:chemistry*; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry; D006360:Heat-Shock Proteins / Q000737:chemistry*; D008954:Models, Biological; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry; D008968:Molecular Conformation; D011485:Protein Binding; D011489:Protein Denaturation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D016963:Thermus thermophilus / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; C070972:HsP104 protein, S cerevisiae; D049071:Endopeptidase Clp; C063842:dnaK protein, E coli; C069775:ClpB protein, E coli