Reconfiguration of the proteasome during chaperone-mediated assembly

Soyeon Park, Xueming Li, Ho Min Kim, Chingakham Ranjit Singh, Geng Tian, Martin A. Hoyt, Scott Lovell, Kevin P. Battaile, Michal Zolkiewski, Philip Coffino, Jeroen Roelofs, Yifan Cheng, Daniel Finley

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

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 carboxy-terminal tails inserting into pockets of the α-ring. Rpt ring assembly is mediated by four chaperones, each binding a distinct Rpt subunit. Here we report that the base subassembly of the Saccharomyces cerevisiae 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 non-hydrolysable ATP analogue, 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 proteasomes, 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.

Original languageEnglish (US)
Pages (from-to)512-516
Number of pages5
JournalNature
Volume497
Issue number7450
DOIs
StatePublished - 2013

All Science Journal Classification (ASJC) codes

  • General

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