Dissecting β-ring assembly pathway of the mammalian 20S proteasome

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Abstract
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.