Journal ArticleDOI
Crystal structure of the 20S proteasome from the archaeon T. acidophilum at 3.4 A resolution.
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TLDR
The three-dimensional structure of the proteasome from the archaebacterium Thermoplasma acidophilum has been elucidated by x-ray crystallographic analysis by means of isomorphous replacement and cyclic averaging.Abstract:
The three-dimensional structure of the proteasome from the archaebacterium Thermoplasma acidophilum has been elucidated by x-ray crystallographic analysis by means of isomorphous replacement and cyclic averaging. The atomic model was built and refined to a crystallographic R factor of 22.1 percent. The 673-kilodalton protease complex consists of 14 copies of two different subunits, alpha and beta, forming a barrel-shaped structure of four stacked rings. The two inner rings consist of seven beta subunits each, and the two outer rings consist of seven alpha subunits each. A narrow channel controls access to the three inner compartments. The alpha 7 beta 7 beta 7 alpha 7 subunit assembly has 72-point group symmetry. The structures of the alpha and beta subunits are similar, consisting of a core of two antiparallel beta sheets that is flanked by alpha helices on both sides. The binding of a peptide aldehyde inhibitor marks the active site in the central cavity at the amino termini of the beta subunits and suggests a novel proteolytic mechanism.read more
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The Ubiquitin System
Avram Hershko,Aaron Ciechanover +1 more
TL;DR: This review discusses recent information on functions and mechanisms of the ubiquitin system and focuses on what the authors know, and would like to know, about the mode of action of ubi...
Journal ArticleDOI
The Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction
TL;DR: It is clear now that degradation of cellular proteins is a highly complex, temporally controlled, and tightly regulated process that plays major roles in a variety of basic pathways during cell life and death as well as in health and disease.
Journal ArticleDOI
Structure of 20S proteasome from yeast at 2.4 A resolution.
Michael Groll,Lars Ditzel,Jan Löwe,Daniela Stock,Matthias Bochtler,Hans D. Bartunik,Robert Huber +6 more
TL;DR: Two β-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.
Journal ArticleDOI
The 26S Proteasome: A Molecular Machine Designed for Controlled Proteolysis
TL;DR: In eukaryotic cells, most proteins in the cytosol and nucleus are degraded via the ubiquitin-proteasome pathway, and the 26S proteasome is a 2-MDa molecular machine built from approximately 31 different subunits, which catalyzes protein degradation.
Journal ArticleDOI
Recognition of the polyubiquitin proteolytic signal.
TL;DR: The properties of the substrates studied here implicate substrate unfolding as a kinetically dominant step in the proteolysis of properly folded proteins, and suggest that extraproteasomal chaperones are required for efficient degradation of certain proteasome substrates.
References
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Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features
Wolfgang Kabsch,Chris Sander +1 more
TL;DR: A set of simple and physically motivated criteria for secondary structure, programmed as a pattern‐recognition process of hydrogen‐bonded and geometrical features extracted from x‐ray coordinates is developed.
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MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures
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Accurate Bond and Angle Parameters for X-ray Protein Structure Refinement
Richard A. Engh,Robert Huber +1 more
TL;DR: In this article, a statistical survey of X-ray structures of small compounds from the Cambridge Structural Database is used for the refinement of protein structures determined by X-Ray crystallography.
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Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules
Kenneth L. Rock,Colette F. Gramm,Lisa Rothstein,Karen Clark,Ross L. Stein,Lawrence Dick,Daniel Hwang,Alfred L. Goldberg +7 more
TL;DR: Peptide aldehydes that inhibit major peptidase activities of the 20S and 26S proteasomes are shown to reduce the degradation of protein and ubiquitinated protein substrates by 26S particles.
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Raster3D Version 2.0. A program for photorealistic molecular graphics.
TL;DR: Raster3D Version 2.0 is a program suite for the production of photorealistic molecular graphics images, and is particularly suited for use in producing large raster images of macromolecules for output to a film recorder or high-quality color printer.