The 20S proteasome is the catalytic core of the 26S proteasome. It comprises four stacked rings of seven subunits each, α1–7β1–7β1–7α1–7. Recent studies indicated that proteasome-specific chaperones and β-subunit appendages assist in the formation of α-rings and dimerization of half-proteasomes, but the process involved in the assembly of β-rings is poorly understood. Here, we clarify the mechanism of β-ring formation on α-rings by characterizing assembly intermediates accumulated in cells depleted of each β-subunit. Starting from β2, incorporation of β-subunits occurs in an orderly manner dependent on the propeptides of β2 and β5, and the C-terminal tail of β2. Unexpectedly, hUmp1, a chaperone functioning at the final assembly step, is incorporated as early as β2 and is required for the structural integrity of early assembly intermediates. We propose a model in which β-ring formation is assisted by both intramolecular and extrinsic chaperones, whose roles are partially different between yeast and mammals.
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