The base of the proteasome regulatory particle exhibits chaperone-like activity

Beate C. Braun, Michael Glickman, Regine Kraft, Burkhardt Dahlmann, Peter M. Kloetzel, Daniel Finley, Marion Schmidt

Research output: Contribution to journalArticlepeer-review

391 Scopus citations


Protein substrates of the proteasome must apparently be unfolded and translocated through a narrow channel to gain access to the proteolytic active sites of the enzyme. Protein folding in vivo is mediated by molecular chaperones. Here, to test for chaperone activity of the proteasome, we assay the reactivation of denatured citrate synthase. Both human and yeast proteasomes stimulate the recovery of the native structure of citrate synthase. We map this chaperone-like activity to the base of the regulatory particle of the proteasome, that is, to the ATPase-containing assembly located at the substrate-entry ports of the channel. Denatured but not native citrate synthase is bound by the base complex. Ubiquitination of citrate synthase is not required for its binding or refolding by the base complex of the proteasome. These data suggest a model in which ubiquitin-protein conjugates are initially tethered to the proteasome by specific recognition of their ubiquitin chains; this step is followed by a nonspecific interaction between the base and the target protein, which promotes substrate unfolding and translocation.

Original languageEnglish (US)
Pages (from-to)221-226
Number of pages6
JournalNature Cell Biology
Issue number4
StatePublished - Aug 1999
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology


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