Structure and structure formation of the 20S proteasome

Abstract

Eukaryotic 20S proteasomes are complex oligomeric proteins. The maturation process of the 14 different α- and β-subunits has to occur in a highly coordinate manner. In addition β-subunits are synthesized as proproteins and correct processing has to be guaranteed during complex maturation. The structure formation can be subdivided in different phases. The knowledge of the individual phases is summarized in this publication. As a first step the newly synthesized monomers have to adopt the correct tertiary structure, a process that might be supported in the case of the β-subunits by the intramolecular chaperone activity postulated for the prosequences. Subsequently the α-subunits form ring-like structures thereby providing docking sites for the different β-subunits. The result most likely is a double ring structure (13S precursor) representing half-proteasomes, which contain immature proproteins. Two 13S precursors associate to form the proteolytically inactive 16S assembly intermediate which still contains unprocessed β-monomers. In addition the chaperone Hsc73 is present within these particles suggesting an essential role during the structure formation process. The processing of monomers with an N-terminal threonine occurs within the 16S particles and is achieved autocatalytically by two subsequent processing events finally leading to the mature, active 20S proteasome.