Reconfiguration of the proteasome during chaperone-mediated assembly
Kim, Ho Min
Singh, Chingakham Ranjit
Hoyt, Martin A.
Nature Publishing Group
Scholarly/refereed, author accepted manuscript
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The proteasomal ATPase ring, comprising Rpt1-Rpt6, associates with the heptameric α ring of the proteasome core particle (CP) in the mature proteasome, with the Rpt C-terminal tails inserting into pockets of the α ring1–4. Rpt ring assembly is mediated by four chaperones, each binding a distinct Rpt subunit5–10. We report that the base subassembly of the proteasome, which includes the Rpt ring, forms a high affinity complex with the CP. This complex is subject to active dissociation by the chaperones Hsm3, Nas6, and Rpn14. Chaperone-mediated dissociation was abrogated by a nonhydrolyzable ATP analog, indicating that chaperone action is coupled to nucleotide hydrolysis by the Rpt ring. Unexpectedly, synthetic Rpt tail peptides bound α pockets with poor specificity, except for Rpt6, which uniquely bound the α2/α3 pocket. Although the Rpt6 tail is not visualized within an α pocket in mature proteasomes2–4, it inserts into the α2/α3 pocket in the base-CP complex and is important for complex formation. Thus, the Rpt-CP interface is reconfigured when the lid complex joins the nascent proteasome to form the mature holoenzyme.
Park, S., Li, X., Kim, H. M., Singh, C. R., Tian, G., Hoyt, M. A., … Finley, D. (2013). Reconfiguration of the proteasome during chaperone-mediated assembly. Nature, 497(7450), 512–516. http://doi.org/10.1038/nature12123
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