Crowbars and ratchets: hsp100 chaperones as tools in reversing protein aggregation.
Molecular chaperones have the capacity to prevent inappropriate interactions between aggregation-prone folding or unfolding intermediates created in the cell during protein synthesis or in response to physical and chemical stress. What happens when surveillance by molecular chaperones is evaded or overwhelmed and aggregates accumulate? Recent progress in the elucidation of Hsp100/Clp function suggests that intracellular aggregates or stable complexes can be progressively dissolved by the action of chaperones that act as molecular crowbars or ratchets. These insights set the stage for new progress in the understanding and treatment of diseases of protein folding.
Glover
J R
JR
Department of Biochemistry, University of Toronto, ON, Canada. john.glover@utoronto.ca
Tkach
J M
JM
D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000737:chemistry; D000682:Amyloid / Q000737:chemistry; D000818:Animals; D002470:Cell Survival; D003062:Codon; D049071:Endopeptidase Clp; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D015800:Protozoan Proteins / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D012697:Serine Endopeptidases / Q000737:chemistry; D013314:Stress, Mechanical
D000682:Amyloid; D003062:Codon; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D015800:Protozoan Proteins; D029701:Saccharomyces cerevisiae Proteins; C070972:HsP104 protein, S cerevisiae; D012697:Serine Endopeptidases; D049071:Endopeptidase Clp; D000251:Adenosine Triphosphatases; C095049:ClpB protein, Leishmania; C088072:ClpX protein, E coli; D000074183:ATPases Associated with Diverse Cellular Activities