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Forging a proteasome α-ring with dedicated proteasome chaperones

Nature Structural & Molecular Biology volume 15, pages 218–220 (2008)Cite this article

Assembly of the 34-subunit, 2.5 megadalton 26S proteasome starts with formation of the seven-membered α-ring. A set of newly identified proteasome chaperones serves as a clamp to seal α-rings with the correct composition. By regulating the efficiency and outcome of this crucial step in proteasome biogenesis, these dedicated proteasome chaperones apparently partake in the stress response and in adaptation to intracellular proteolysis needs.

On pages 228 and 237 of this issue, two elegant studies show that proteasome assembly in eukaryotes begins with the formation of a complete α-ring5,6. The correct composition of this primary intermediate is guaranteed by two sets of proteasome chaperones. Pac1–Pac2 (or Pba1–Pba2) dimers attach to individual α subunits and help to orientate them into the correct order1,3,4. In parallel, a dimer of Pba3–Pba4 binds to α5 in the initial stages of α-ring formation5,6 and presumably helps to seal the α-ring by precisely prioritizing the entry of the very last α subunits, α4 and α3 (Fig. 2). However, their task is not over yet. Pac1–Pac2 remains attached to the α-ring, blocking nonproductive homodimerization until after maturation of the 20S CP, by which they are degraded1. The second chaperone set, Pba3–Pba4, may remain attached to the completed α-ring on the opposing surface6. Halfway through completion of the β-ring (the 13S complex), Pba3–Pba4 is released (due to steric hindrance from β4)6 and recycled4,5. The next subunit, β5, can occupy the slot vacated upon Pba3–Pba4 release. Interestingly, β subunits share a certain structural similarity with the Pba3–Pba4 complex, which may explain their common site of attachment on the α-ring template6.

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Figure 1: Chaperone-facilitated eukaryotic proteasome assembly.
Figure 2: The α-ring as a template for the stacked 20S barrel.
Figure 3: Pba3–Pba4 as an α-ring clamp.

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Authors and Affiliations

  1. Rina Rosenzweig and Michael H. Glickman are in the Department of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel. glickman@tx.technion.ac.il,

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Rosenzweig, R., Glickman, M. Forging a proteasome α-ring with dedicated proteasome chaperones. Nat Struct Mol Biol 15, 218–220 (2008). https://doi.org/10.1038/nsmb0308-218

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