Polyubiquitin substrates allosterically activate their own degradation by the 26S proteasome


The 26S proteasome degrades polyubiquitylated (polyUb) proteins by an ATP-dependent mechanism. Here we show that binding of model polyUb substrates to the 19S regulator of mammalian and yeast 26S proteasomes enhances the peptidase activities of the 20S proteasome about two-fold in a process requiring ATP hydrolysis. Monoubiquitylated proteins or tetraubiquitin alone exert no effect. However, 26S proteasomes from the yeast alpha3DeltaN open-gate mutant and the rpt2YA and rpt5YA mutants with impaired gating can still be activated (approximately 1.3-fold to 1.8-fold) by polyUb-protein binding. Thus, binding of polyUb substrates to the 19S regulator stabilizes gate opening of the 20S proteasome and induces conformational changes of the 20S proteasome that facilitate channeling of substrates and their access to active sites. In consequence, polyUb substrates will allosterically stimulate their own degradation.


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Nat. Struct. Mol. Biol.
Nat. Struct. Mol. Biol. 16(2): 219-25
25th Jan 2009

Dawadschargal Bech-Otschir, Annett Helfrich, Cordula Enenkel, Gesa Consiglieri, Michael Seeger, Hermann-Georg Holzhütter, Burkhardt Dahlmann, Peter-Michael Kloetzel

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[Hermann-Georg Holzhütter]

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  • Created: 4th Jan 2013 at 12:53
  • Last updated: 24th Oct 2013 at 16:21

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