A multimeric assembly factor controls the formation of alternative 20S proteasomes.
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.
Kusmierczyk
Andrew R
AR
Department of Molecular Biophysics & Biochemistry, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06520-8114, USA.
Kunjappu
Mary J
MJ
Funakoshi
Minoru
M
Hochstrasser
Mark
M
D019295:Computational Biology; D019216:Metals, Heavy / Q000633:toxicity; D008954:Models, Biological; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*
C527523:IRC25 protein, S cerevisiae; D019216:Metals, Heavy; D018832:Molecular Chaperones; D009097:Multienzyme Complexes; D050505:Mutant Proteins; C527522:POC4 protein, S cerevisiae; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D046988:Proteasome Endopeptidase Complex