Kusmierczyk Andrew R, Kunjappu Mary J, Funakoshi Minoru, Hochstrasser Mark
Department of Molecular Biophysics & Biochemistry, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06520-8114, USA.
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.
蛋白酶体是真核细胞的核心调节蛋白酶。异源七聚体α亚基环和β亚基环堆叠形成20S蛋白酶体，其与19S调节颗粒（RP）结合。我们在此表明，两种酵母蛋白Pba3和Pba4形成了一种先前未被识别的20S蛋白酶体组装伴侣。Pba3 - Pba4在遗传和物理上与特定的蛋白酶体α亚基相互作用，Pba3 - Pba4的缺失会导致细胞蛋白酶体数量减少和重塑。值得注意的是，突变细胞中积累的蛋白酶体中，α4亚基的第二个拷贝取代了α3。20S蛋白酶体组装缺陷也与RP组装改变有关；这一意外结果表明，20S蛋白酶体在体内可作为RP组装因子发挥作用。我们的数据表明，Pba3 - Pba4协调特定类型蛋白酶体的形成，这是控制替代性蛋白酶体复合物组装的反式作用因子的首个例子。
