A multimeric assembly factor controls the formation of alternative 20S proteasomes

Nat Struct Mol Biol. 2008 Mar;15(3):237-44. doi: 10.1038/nsmb.1389. Epub 2008 Feb 17.


The proteasome is the central regulatory protease of eukaryotic cells. Heteroheptameric alpha-subunit and beta-subunit rings stack to form the 20S proteasome, which associates with a 19S regulatory particle (RP). Here we show that two yeast proteins, Pba3 and Pba4, form a previously unidentified 20S proteasome-assembly chaperone. Pba3-Pba4 interacts genetically and physically with specific proteasomal alpha subunits, and loss of Pba3-Pba4 causes both a reduction and a remodeling of cellular proteasomes. Notably, mutant cells accumulate proteasomes in which a second copy of the alpha4 subunit replaces alpha3. 20S proteasome-assembly defects also are associated with altered RP assembly; this unexpected result suggests that the 20S proteasome can function as an RP-assembly factor in vivo. Our data demonstrate that Pba3-Pba4 orchestrates formation of a specific type of proteasome, the first example of a trans-acting factor that controls assembly of alternative proteasomal complexes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computational Biology
  • Metals, Heavy / toxicity
  • Models, Biological
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / metabolism*
  • Multienzyme Complexes / chemistry
  • Multienzyme Complexes / metabolism
  • Mutant Proteins / chemistry
  • Mutant Proteins / metabolism
  • Mutation / genetics
  • Proteasome Endopeptidase Complex / chemistry
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Binding / drug effects
  • Protein Structure, Secondary
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*


  • IRC25 protein, S cerevisiae
  • Metals, Heavy
  • Molecular Chaperones
  • Multienzyme Complexes
  • Mutant Proteins
  • POC4 protein, S cerevisiae
  • Protein Subunits
  • Saccharomyces cerevisiae Proteins
  • Proteasome Endopeptidase Complex