Blm10 protein promotes proteasomal substrate turnover by an active gating mechanism

Thomas Dange, David Smith, Tahel Noy, Philipp C. Rommel, Lukas Jurzitza, Radames J.B. Cordero, Anne Legendre, Daniel Finley, Alfred L. Goldberg, Marion Schmidt

Research output: Contribution to journalArticle

Abstract

For optimal proteolytic function, the central core of the proteasome (core particle (CP) or 20S) has to associate with activators. Weinvestigated the impact of the yeast activator Blm10 on proteasomal peptide and protein degradation. We found enhanced degradation of peptide substrates in the presence of Blm10 and demonstrated that Blm10 has the capacity to accelerate proteasomal turnover of the unstructured protein tau-441 in vitro. Mechanistically, proteasome activation requires the opening of a closed gate, which allows passage of unfolded proteins into the catalytic chamber. Our data indicate that gate opening by Blm10 is achieved via engagement of its C-terminal segment with the CP. Crucial for this activity is a conserved C-terminal YYX motif, with the penultimate tyrosine playing a preeminent role. Thus, Blm10 utilizes a gate opening strategy analogous to the proteasomal ATPases HbYX-dependent mechanism. Because gating incompetent Blm10 C-terminal point mutants confers a loss of function phenotype, we propose that the cellular function of Blm10 is based on CP association and activation to promote the degradation of proteasome substrates.

Original languageEnglish (US)
Pages (from-to)42830-42839
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number50
DOIs
StatePublished - Dec 16 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Dange, T., Smith, D., Noy, T., Rommel, P. C., Jurzitza, L., Cordero, R. J. B., Legendre, A., Finley, D., Goldberg, A. L., & Schmidt, M. (2011). Blm10 protein promotes proteasomal substrate turnover by an active gating mechanism. Journal of Biological Chemistry, 286(50), 42830-42839. https://doi.org/10.1074/jbc.M111.300178