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PMID:22025621

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Citation

Dange, T, Smith, D, Noy, T, Rommel, PC, Jurzitza, L, Cordero, RJ, Legendre, A, Finley, D, Goldberg, AL and Schmidt, M (2011) Blm10 protein promotes proteasomal substrate turnover by an active gating mechanism. J. Biol. Chem. 286:42830-9

Abstract

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.

Links

PubMed PMC3234834 Online version:10.1074/jbc.M111.300178

Keywords

Phenotype; Proteasome Endopeptidase Complex/genetics; Proteasome Endopeptidase Complex/metabolism; Protein Binding; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

YEAST:BLM10

enables

GO:0016504: peptidase activator activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

YEAST:BLM10

involved_in

GO:0061136: regulation of proteasomal protein catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

YEAST:BLM10

enables

GO:0070628: proteasome binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

YEAST:BLM10

enables

GO:0070628: proteasome binding

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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