Heterohexameric ring arrangement of the eukaryotic proteasomal ATPases: implications for proteasome structure and assembly.

The proteasome has a paramount role in eukaryotic cell regulation. It consists of a proteolytic core particle (CP) bound to one or two regulatory particles (RPs). Each RP is believed to include six different AAA+ ATPases in a heterohexameric ring that binds the CP while unfolding and translocating substrates into ...
the core. No atomic-resolution RP structures are available. Guided by crystal structures of related homohexameric prokaryotic ATPases, we use disulfide engineering to show that the eukaryotic ATPases form a ring with the arrangement Rpt1-Rpt2-Rpt6-Rpt3-Rpt4-Rpt5 in fully assembled proteasomes. The arrangement is consistent with known assembly intermediates. This quaternary organization clarifies the functional overlap of specific RP assembly chaperones and led us to identify a potential RP assembly intermediate that includes four ATPases (Rpt6-Rpt3-Rpt4-Rpt5) and their cognate chaperones (Rpn14, Nas6, and Nas2). Finally, the ATPase ring structure casts light on alternative RP structural models and the mechanism of RP action.
Mesh Terms:
Adenosine Triphosphatases, Cysteine, Disulfides, Fungal Proteins, Models, Molecular, Molecular Chaperones, Multiprotein Complexes, Mutation, Proteasome Endopeptidase Complex, Protein Engineering, Protein Multimerization, Protein Structure, Quaternary, Structure-Activity Relationship, Yeasts
Mol. Cell
Date: May. 14, 2010
Download Curated Data For This Publication
103071
Switch View:
  • Interactions 14