Crystal Structure of the 20 S Proteasome from the Archaeon T. acidophilum at 3.4 Å Resolution

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.

Structural Insights into the Conformational Diversity of ClpP from Bacillus subtilis

“…All of these protease components are self-compartmentalized proteases that possess catalytic residues located deep inside the molecule, and which are shielded from direct access from the outside. It is unknown how the hydrolyzed products generated inside the protease chamber are efficiently released since all atomic resol-ution structures of HslV, ClpP and the 20S proteasome show virtually no product exit site except for the entrance pores (Bochtler et al, 1999;Groll et al, 1997;Lowe et al, 1995;Song et al, 2000;2003;Sousa et al, 2000;Wang et al, 1997;2001;Yu and Houry, 2007).…”

NMR Spectroscopy of Soluble Protein Complexes at One Mega‐Dalton and Beyond

“…[18] Theoretical rotational correlation times τ c were estimated with the program Hydro-NMR. [19] PDB entries 1PMA [20] and 1YA7 [21] were used for the estimations. The calculations were run for a temperature of 30 °C and the corresponding viscosity of water (0.798×10 -2 Poise).…”

Proteasome inhibitors mechanism; source for design of newer therapeutic agents

“…The complex biochemical mechanism of the proteasome was understood by the determination of its three-dimensional structure. The first structure was obtained for the archaebacterial form of the proteasome 10,11 and revealed a complex, comprising a single a-and btype subunit each repeated 14 times, to create a highly symmetrical core complex. In contrast, the core of the yeast proteasome is made up of seven distinct a-and b-type subunits each repeated twice in the complex.…”