Article
- The EMBO Journal (2007) 26, 2339 - 2349
- doi:10.1038/sj.emboj.7601681
Published online: 12 April 2007
Subject Category:
-Subunit appendages promote 20S proteasome assembly by overcoming an Ump1-dependent checkpoint
Xia Li1, Andrew R Kusmierczyk1, Peter Wong2, Andrew Emili2 and Mark Hochstrasser1
- Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA
- Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada
Correspondence to:
Mark Hochstrasser, Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06520-8114, USA. Tel.: +1 203 432 5101; Fax: +1 203 432 5175; E-mail: Mark.Hochstrasser@Yale.edu
Received 23 November 2006; Accepted 14 March 2007
Abstract
Proteasomes are responsible for most intracellular protein degradation in eukaryotes. The 20S proteasome comprises a dyad-symmetric stack of four heptameric rings made from 14 distinct subunits. How it assembles is not understood. Most subunits in the central pair of 
-subunit rings are synthesized in precursor form. Normally, the 5 (Doa3) propeptide is essential for yeast proteasome biogenesis, but overproduction of 7 (Pre4) bypasses this requirement. Bypass depends on a unique 7 extension, which contacts the opposing ring. The resulting proteasomes appear normal but assemble inefficiently, facilitating identification of assembly intermediates. Assembly occurs stepwise into precursor dimers, and intermediates contain the Ump1 assembly factor and a novel complex, Pba1–Pba2. 7 incorporation occurs late and is closely linked to the association of two half-proteasomes. We propose that dimerization is normally driven by the 5 propeptide, an intramolecular chaperone, but 7 addition overcomes an Ump1-dependent assembly checkpoint and stabilizes the precursor dimer.
Keywords:
- proteasome,
- ubiquitin
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