title: Differential global structural changes in the core particle of yeast and mouse proteasome induced by ligand binding.
abstract: Two clusters of configurations of the main proteolytic subunit β5 were identified by principal component analysis of crystal structures of the yeast proteasome core particle (yCP). The apo-cluster encompasses unliganded species and complexes with nonpeptidic ligands, and the pep-cluster comprises complexes with peptidic ligands. The murine constitutive CP structures conform to the yeast system, with the apo-form settled in the apo-cluster and the PR-957 (a peptidic ligand) complex in the pep-cluster. In striking contrast, the murine immune CP classifies into the pep-cluster in both the apo and the PR-957-liganded species. The two clusters differ essentially by multiple small structural changes and a domain motion enabling enclosure of the peptidic ligand and formation of specific hydrogen bonds in the pep-cluster. The immune CP species is in optimal peptide binding configuration also in its apo form. This favors productive ligand binding and may help to explain the generally increased functional activity of the immunoproteasome. Molecular dynamics simulations of the representative murine species are consistent with the experimentally observed configurations. A comparison of all 28 subunits of the unliganded species with the peptidic liganded forms demonstrates a greatly enhanced plasticity of β5 and suggests specific signaling pathways to other subunits.
authors: Emeritus Group Structure Research, Max Planck Institut für Biochemie, 82152 Martinsried, Germany;Center for Integrated Protein Science at the Department Chemie, Lehrstuhl für Biochemie, Technische Unversität München, 85748 Garching, Germany; castro@biochem.mpg.de huber@biochem.mpg.de.
authors: Marcelino
authors: M
authors: Arciniega
authors: Center for Integrated Protein Science at the Department Chemie, Lehrstuhl für Biochemie, Technische Unversität München, 85748 Garching, Germany;
authors: Philipp
authors: P
authors: Beck
authors: Biomolecular NMR and Munich Center for Integrated Protein Science, Lehrstuhl für Chemie, Technische Universität München, 85747 Garching, Germany;
authors: Oliver F
authors: OF
authors: Lange
authors: Center for Integrated Protein Science at the Department Chemie, Lehrstuhl für Biochemie, Technische Unversität München, 85748 Garching, Germany;
authors: Michael
authors: M
authors: Groll
authors: Emeritus Group Structure Research, Max Planck Institut für Biochemie, 82152 Martinsried, Germany;Center for Integrated Protein Science at the Department Chemie, Lehrstuhl für Biochemie, Technische Unversität München, 85748 Garching, Germany;Zentrum für Medizinische Biotechnologie, Universität Duisburg-Essen, 45117 Essen, Germany; andSchool of Biosciences, Cardiff University, Cardiff CF10 3US, Wales, United Kingdom castro@biochem.mpg.de huber@biochem.mpg.de.
authors: Robert
authors: R
authors: Huber
mesh_terms: D000818:Animals; D003460:Crystallization; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D009842:Oligopeptides / Q000378:metabolism; D025341:Principal Component Analysis; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry* / Q000276:immunology*; D011485:Protein Binding; D011487:Protein Conformation; D015398:Signal Transduction / Q000235:genetics*; D013045:Species Specificity; D015003:Yeasts
chemical_list: D008024:Ligands; D009842:Oligopeptides; C542291:PR-957; D046988:Proteasome Endopeptidase Complex; C520309:proteasome subunit beta5t, mouse
keywords: 20S proteasome; PCA analysis; allosteric regulation