The ultimate nanoscale mincer: assembly, structure and active sites of the 20S proteasome core

Abstract

20S proteasomes constitute the proteolytic core of large protease complexes found in all branches of life. Among these, the eukaryotic 26S proteasome ubiquitously poses as a vital final entity in regulated degradation of intracellular proteins. The composition of 20S core particles has been disclosed in detail, facilitated by groundbreaking studies on ancestral prokaryotic 20S proteasomes of low complexity and culminated in the crystal structure determination of the much more complex eukaryotic particles. This article first summarizes insights into the structural organization of the 20S core followed by characterization of its proteolytic activities, which are confined to the central cavity of the particle. In eukaryotes they reside in three different subunit types differing in their preference for cleavage sites in substrates as well as in their importance for the proteasome's cellular function. The second part reviews current knowledge on the biogenesis pathways of 20S core particles, which have to ensure not only the fixed subunit arrangement but also activation of proteolytic subunits in a late assembly state.