Proteasomes: structure and biology

Abstract

The proteasome is a multisubunit protease complex with an apparent sedimentation coefficient of 20S. Two types of regulatory complexes, named PA700 and PA28, bind to both ends of the cylindrical 20S proteasome to form the dumbbell-like and football-like proteasomes, respectively. The former complex, named the 26S proteasome, is a eukaryotic ATP-dependent protease and appears to be well organized as a large complex of 2 MDa, consisting of approximately 40 polypeptides, to facilitate rapid proteolysis. It is assumed to be a protein "death machine", destroying a variety of cellular proteins that have acquired a specific degradation signal(s) such as a multiubiquitin chain. Recently data on in vivo substrates for the ubiquitin-proteasome pathway have been accumulating rapidly, implying its involvement in many biologically important processes, such as cell-cycle regulation, signal transduction, protein quality control, and the immune response. The newly-identified PA28 family proteins are inducible by interferons, and may cooperate with the 26S proteasome or play additional roles. Since the proteasome is capable of catalyzing breakdown of proteins not only irreversibly, but also rapidly and timely, it is thought to be a new regulatory system for biological reactions in eukaryotes.