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ATP hydrolysis-dependent disassembly of the 26S proteasome is part of the catalytic cycle.

ATP hydrolysis is required for degradation of polyubiquitinated proteins by the 26S proteasome but is thought to play no role in proteasomal stability during the catalytic cycle. In contrast to this view, we report that ATP hydrolysis triggers rapid dissociation of the 19S regulatory particles from immunopurified 26S complexes in a manner coincident with release of the bulk of proteasome-interacting proteins. Strikingly, this mechanism leads to quantitative disassembly of the 19S into subcomplexes and free Rpn10, the polyubiquitin binding subunit. Biochemical reconstitution with purified Sic1, a prototype substrate of the Cdc34/SCF ubiquitin ligase, suggests that substrate degradation is essential for triggering the ATP hydrolysis-dependent dissociation and disassembly of the 19S and that this mechanism leads to release of degradation products. This is the first demonstration that a controlled dissociation of the 19S regulatory particles from the 26S proteasome is part of the mechanism of protein degradation.

Pubmed ID: 15907469

Authors

  • Babbitt SE
  • Kiss A
  • Deffenbaugh AE
  • Chang YH
  • Bailly E
  • Erdjument-Bromage H
  • Tempst P
  • Buranda T
  • Sklar LA
  • Baumler J
  • Gogol E
  • Skowyra D

Journal

Cell

Publication Data

May 20, 2005

Associated Grants

  • Agency: NIBIB NIH HHS, Id: EB 00264
  • Agency: NIGMS NIH HHS, Id: GM 54703
  • Agency: NIGMS NIH HHS, Id: GM 65267
  • Agency: NIAID NIH HHS, Id: K25 AI 060036
  • Agency: NIAID NIH HHS, Id: K25 AI060036
  • Agency: NCI NIH HHS, Id: P30 CA 08748

Mesh Terms

  • Adenosine Triphosphatases
  • Adenosine Triphosphate
  • Anaphase-Promoting Complex-Cyclosome
  • Carrier Proteins
  • Catalysis
  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Endopeptidases
  • Hydrolysis
  • Microscopy, Electron
  • Proteasome Endopeptidase Complex
  • Protein Subunits
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin
  • Ubiquitin-Conjugating Enzymes
  • Ubiquitin-Protein Ligase Complexes