Dynamic Regulation of Archaeal Proteasome Gate Opening As Studied by TROSY NMR

• Published in: Science (American Association for the Advancement of Science) Vol. 328; no. 5974; pp. 98 - 102
• Main Authors: Religa, Tomasz L, Sprangers, Remco, Kay, Lewis E
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 02.04.2010; The American Association for the Advancement of Science
• Subjects: Amides; Archaeal Proteins - chemistry; Archaeal Proteins - genetics; Archaeal Proteins - metabolism; Bacteria; Biochemistry; Biological and medical sciences; Catalysis; Conformational dynamics in molecular biology; Correlations; Electron Spin Resonance Spectroscopy; Endopeptidases - chemistry; Endopeptidases - genetics; Endopeptidases - metabolism; Fundamental and applied biological sciences. Psychology; Hydrolysis; Magnetic spectroscopy; Models, Molecular; Molecular biology; Molecular biophysics; Monomers; Mutant Proteins - chemistry; Mutant Proteins - metabolism; Nuclear magnetic resonance; Nuclear Magnetic Resonance, Biomolecular; Physiological regulation; Protein Conformation; Protein Structure, Quaternary; Protein Subunits - chemistry; Protein Subunits - metabolism; Proteins; Spectral correlation; Spectrum analysis; Spin Labels; Surface areas; Thermoplasma - chemistry; Thermoplasma - enzymology; Thermoplasma - genetics; Thermoplasma - metabolism; Thermoplasma acidophilum; Peptidases; Multicatalytic endopeptidase complex; Regulation(control); Archaeobacteria; Enzyme; Dynamics; Bacteria; Hydrolases; NMR spectrometry; Thermoplasma acidophilum; Physical method; Conformation
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1184991

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 α 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.