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Autocatalytic processing of the 20S proteasome
E Seemuller1, A Lupas, W Baumeister
1Max-Planck-Institut für Biochemie, Martinsried bei München, Germany.
Nature
|August 1, 1996
Summary
N-terminal (Ntn) hydrolases, like the proteasome, are activated by autocatalytic processing. This study reveals the proteasome
Area of Science:
- Enzymology
- Proteasome Structure and Function
- Biochemistry
Background:
- N-terminal (Ntn) nucleophile hydrolases feature a unique four-layer alpha + beta fold.
- These enzymes utilize their N-terminal residue (cysteine, serine, or threonine) as the catalytic nucleophile.
- Inactive precursors are processed to active enzymes, with autocatalytic processing suggested for Ntn hydrolases.
Purpose of the Study:
- To investigate the mechanism of propeptide processing in the Thermoplasma acidophilum proteasome.
- To determine if proteasome processing is autocatalytic and its mechanism (intermolecular vs. intramolecular).
- To understand the role of specific residues and processing in proteasome assembly and function.
Main Methods:
- Biochemical analysis of propeptide processing in Thermoplasma acidophilum proteasome.
- Investigation of processing dependency on propeptide length and sequence.
- Assessment of processing timing relative to beta-subunit folding.
Main Results:
- Propeptide processing in the Thermoplasma acidophilum proteasome is autocatalytic but likely intermolecular.
- Processing is not essential for assembly and is largely independent of propeptide characteristics.
- Processing occurs prior to the completion of beta-subunit folding.
Conclusions:
- The study elucidates the autocatalytic, likely intermolecular, processing mechanism of the Thermoplasma acidophilum proteasome.
- Threonine is identified as the universally conserved and most functional residue for both proteolysis and processing in proteasome subunits.