Details

Autor(en) / Beteiligte

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

Titel

Blm10 Protein Promotes Proteasomal Substrate Turnover by an Active Gating Mechanism

Ist Teil von

• The Journal of biological chemistry, 2011-12, Vol.286 (50), p.42830-42839

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2011

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• For optimal proteolytic function, the central core of the proteasome (core particle (CP) or 20S) has to associate with activators. We investigated 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. Background: Association of the proteasome core with activators regulates proteasome activity. Results: Blm10 association increases proteasome activity toward peptides and the unstructured proteasome substrate tau-441. This process is mediated by the C terminus of Blm10. Conclusion: C-terminal docking-mediated proteasome activation by Blm10 facilitates the turnover of peptide and protein substrates. Significance: Blm10 contributes to the regulation of proteasome activity.