Park, SoyeonLi, XuemingKim, Ho MinSingh, Chingakham RanjitTian, GengHoyt, Martin A.Lovell, ScottBattaile, Kevin P.Zolkiewski, MichalCoffino, PhilipRoelofs, JeroenCheng, YifanFinley, Daniel2014-03-112013Park, S., X. Li, H. M. Kim, C. R. Singh, G. Tian, M. A. Hoyt, S. Lovell, et al. 2013. “Reconfiguration of the proteasome during chaperone-mediated assembly.” Nature 497 (7450): 10.1038/nature12123. doi:10.1038/nature12123. http://dx.doi.org/10.1038/nature12123.0028-0836http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879146The 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.en-USproteasomechaperonesingle particle cryoEMATPaseJournal Article2014-03-1110.1038/nature12123