From the cradle to the grave: molecular chaperones that may choose between folding and degradation.
Molecular chaperones are known to facilitate cellular protein folding. They bind non-native proteins and orchestrate the folding process in conjunction with regulatory cofactors that modulate the affinity of the chaperone for its substrate. However, not every attempt to fold a protein is successful and chaperones can direct misfolded proteins to the cellular degradation machinery for destruction. Protein quality control thus appears to involve close cooperation between molecular chaperones and energy-dependent proteases. Molecular mechanisms underlying this interplay have been largely enigmatic so far. Here we present a novel concept for the regulation of the eukaryotic Hsp70 and Hsp90 chaperone systems during protein folding and protein degradation.
Höhfeld
J
J
Institut für Zellbiologie, Rheinische Friedrich-Wilhelms-Universität Bonn, Ulrich-Haberland-Strasse 61a, D-53121 Bonn, Germany. hoehfeld@uni-bonn.de
Cyr
D M
DM
Patterson
C
C
D000818:Animals; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D008025:Ligases / Q000378:metabolism; D008954:Models, Biological; D008957:Models, Genetic; D018832:Molecular Chaperones / Q000737:chemistry* / Q000502:physiology*; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D025801:Ubiquitin / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D025801:Ubiquitin; D008025:Ligases