title: Dynamic regulation of archaeal proteasome gate opening as studied by TROSY NMR.
abstract: The proteasome catalyzes the majority of protein degradation in the cell and plays an integral role in cellular homeostasis. Control over proteolysis by the 20S core-particle (CP) proteasome is achieved by gated access of substrate; thus, an understanding of the molecular mechanism by which these gates regulate substrate entry is critical. We used methyl-transverse relaxation optimized nuclear magnetic resonance spectroscopy to show that the amino-terminal residues that compose the gates of the alpha subunits of the Thermoplasma acidophilum proteasome are highly dynamic over a broad spectrum of time scales and that gating termini are in conformations that extend either well inside (closed gate) or outside (open gate) of the antechamber. Interconversion between these conformers on a time scale of seconds leads to a dynamic regulation of 20S CP proteolysis activity.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Tomasz L
authors.initials: TL
authors.lastname: Religa
authors.forename: Remco
authors.initials: R
authors.lastname: Sprangers
authors.forename: Lewis E
authors.initials: LE
authors.lastname: Kay
mesh_terms: D019843:Archaeal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D010450:Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D013113:Spin Labels; D013822:Thermoplasma / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
chemical_list: D019843:Archaeal Proteins; D050505:Mutant Proteins; D021122:Protein Subunits; D013113:Spin Labels; D010450:Endopeptidases; C093138:proteasome, Thermoplasma