Dissecting beta-ring assembly pathway of the mammalian 20S proteasome.
The 20S proteasome is the catalytic core of the 26S proteasome. It comprises four stacked rings of seven subunits each, alpha(1-7)beta(1-7)beta(1-7)alpha(1-7). Recent studies indicated that proteasome-specific chaperones and beta-subunit appendages assist in the formation of alpha-rings and dimerization of half-proteasomes, but the process involved in the assembly of beta-rings is poorly understood. Here, we clarify the mechanism of beta-ring formation on alpha-rings by characterizing assembly intermediates accumulated in cells depleted of each beta-subunit. Starting from beta2, incorporation of beta-subunits occurs in an orderly manner dependent on the propeptides of beta2 and beta5, and the C-terminal tail of beta2. Unexpectedly, hUmp1, a chaperone functioning at the final assembly step, is incorporated as early as beta2 and is required for the structural integrity of early assembly intermediates. We propose a model in which beta-ring formation is assisted by both intramolecular and extrinsic chaperones, whose roles are partially different between yeast and mammals.
Hirano
Yuko
Y
Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Kaneko
Takeumi
T
Okamoto
Kenta
K
Bai
Minghui
M
Yashiroda
Hideki
H
Furuyama
Kaori
K
Kato
Koichi
K
Tanaka
Keiji
K
Murata
Shigeo
S
D002460:Cell Line; D019281:Dimerization; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism
D050883:HSC70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D010455:Peptides; D011498:Protein Precursors; D021122:Protein Subunits; C110856:proteasome maturation protein; D046988:Proteasome Endopeptidase Complex