Structure of 20S proteasome from yeast at 2.4 Å resolution

• Published in: Nature (London) Vol. 386; no. 6624; pp. 463 - 471
• Main Authors: GROLL, M, DITZEL, L, LÖWE, J, STOCK, D, BOCHTLER, M, BARTUNIK, H. D, HUBER, R
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 03-04-1997
• Subjects: Acetylcysteine - analogs & derivatives; Acetylcysteine - pharmacology; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Calpain - antagonists & inhibitors; Crystallography, X-Ray; Cysteine Endopeptidases - chemistry; Cysteine Endopeptidases - drug effects; Cysteine Endopeptidases - metabolism; Endopeptidases - chemistry; Endopeptidases - metabolism; Enzyme Inhibitors - pharmacology; Enzyme Precursors - chemistry; Enzyme Precursors - metabolism; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Glycoproteins - pharmacology; Growth, nutrition, metabolism, transports, enzymes. Molecular biology; Histocompatibility Antigens Class I - metabolism; Hydrolases; Microbiology; Models, Molecular; Multienzyme Complexes - chemistry; Multienzyme Complexes - drug effects; Multienzyme Complexes - metabolism; Mycology; Proteasome Endopeptidase Complex; Protein Conformation; Saccharomyces cerevisiae - enzymology; Thermoplasma - enzymology; Threonine - chemistry; Multicatalytic endopeptidase complex; Yeast; Multienzyme complex; Enzyme; Subunit; Fungi; Peptidases; Hydrolases; Ascomycetes; Saccharomyces cerevisiae; Thallophyta; Structural analysis; Crystalline structure
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/386463a0

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.