ABSTRACT
During the past decade, rapid progress was made in elucidating the 20S proteasome's structure, as well as in establishing its unusual proteolytic mecha nism. This was enormously facilitated by the discovery of ancestral proteasome particles in certain bacterial species which led to the first crystal structure determination of a 20S proteasome. The following X-ray structure analysis of the much more complex yeast 20S proteasome certainly represents the largest breakthrough towards understanding structurefunction relationships of the eukaryotic core particle. Nevertheless, important questions about the mechanism of protein degradation in the 20S particle remained and are subject to ongoing research. Since the proteolytically active sites form autocatalytically during the partic le ’s assembly, c larification of the proteasome maturation pathway has become another major challenge. In the first section of this article I will review, with special emphasis on studies using the yeast system, on the progress made during the current decade in identifying the proteolytic sites, in establishing their specificity and in analyzing their contribution to model substrate degra dation. The second section will introduce the still limited knowledge about the eukaryotic 20S proteasome assembly pathway, for which principles found for the formation of bacterial 2 0 S particles might apply and therefore are summarized as well. Several recent reviews cover both main topics of this article to various
extent1 ' 5 and are recommended for further details. A comprehensive description of bacterial proteasomes is given in Chapter 2 by Zwickl et al, and general structural aspects are presented in more detail in Chapter 3 by Bochtler et al. I will only briefly touch the role of proteasomal activity in antigen presentation, because this is the topic of Chapter 21 by Kloetzel and Kuckelkorn.
