Structure of 20S proteasome from yeast at 2.4Å resolution

Abstract

The crystal structure of the 20S proteasome from the yeast Saccharomyces cerevisiae shows that its 28 protein subunits are arranged as an (alpha1...alpha7, beta1...beta7)2 complex in four stacked rings and occupy unique locations. The interior of the particle, which harbours the active sites, is only accessible by some very narrow side entrances. The beta-type subunits are synthesized as proproteins before being proteolytically processed for assembly into the particle. The proforms of three of the seven different beta-type subunits, beta1/PRE3, beta2/PUP1 and beta5/PRE2, are cleaved between the threonine at position 1 and the last glycine of the pro-sequence, with release of the active-site residue Thr 1. These three beta-type subunits have inhibitor-binding sites, indicating that PRE2 has a chymotrypsin-like and a trypsin-like activity and that PRE3 has peptidylglutamyl peptide hydrolytic specificity. Other beta-type subunits are processed to an intermediate form, indicating that an additional nonspecific endopeptidase activity may exist which is important for peptide hydrolysis and for the generation of ligands for class I molecules of the major histocompatibility complex.

Intracellular Dynamics of the Ubiquitin-Proteasome-System

“…With a molecular mass of 700 kDa, the CP is composed of seven distinct α and β subunits, each of which form heptameric rings stacked into a barrel composed of two outer α rings and two inner β rings ( Groll et al , 1997). The maturation of the CP involves the dimerization of two inactive precursor complexes, resembling two half-CPs.…”

Structural Insights into the Conformational Diversity of ClpP from Bacillus subtilis

“…All of these protease components are self-compartmentalized proteases that possess catalytic residues located deep inside the molecule, and which are shielded from direct access from the outside. It is unknown how the hydrolyzed products generated inside the protease chamber are efficiently released since all atomic resol-ution structures of HslV, ClpP and the 20S proteasome show virtually no product exit site except for the entrance pores (Bochtler et al, 1999;Groll et al, 1997;Lowe et al, 1995;Song et al, 2000;2003;Sousa et al, 2000;Wang et al, 1997;2001;Yu and Houry, 2007).…”

Bioinformatic analysis of functional differences between the immunoproteasome and the constitutive proteasome

“…The 20S proteasome consists of 14 different protein subunits (Groll et al1997), of which only three have an active site (Groll et al 1997(Groll et al , 1999Heinemeyer et al 1997;Tanaka and Kasahara 1998) Tanaka and Kasahara 1998). Thus two forms of proteasome exist: the "immunoproteasome", which is expressed in cells stimulated by gamma interferon (IFN-g) or tumor necrosis factor alpha (TNF-a), and in primary and secondary lymphoid organs, and the "constitutive proteasome", which is expressed in healthy, normal tissues and in immune-privileged organs such as the brain (Dahlmann et al 2000;Noda et al 2000;Kuckelkorn et al 2002).…”