TY - JOUR
T1 - Blm10 protein promotes proteasomal substrate turnover by an active gating mechanism
AU - Dange, Thomas
AU - Smith, David
AU - Noy, Tahel
AU - Rommel, Philipp C.
AU - Jurzitza, Lukas
AU - Cordero, Radames J.B.
AU - Legendre, Anne
AU - Finley, Daniel
AU - Goldberg, Alfred L.
AU - Schmidt, Marion
PY - 2011/12/16
Y1 - 2011/12/16
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M111.300178
DO - 10.1074/jbc.M111.300178
M3 - Article
C2 - 22025621
AN - SCOPUS:83355169695
SN - 0021-9258
VL - 286
SP - 42830
EP - 42839
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 50
ER -