Rearrangement of the 16S precursor subunits is essential for the formation of the active 20S proteasome

¹ Univ of texas
² Univ of Texas
³ Charite, Berlin

^* To whom correspondence should be addressed. E-mail: pawel.a.penczek{at}uth.tmc.edu.

Submitted on August 5, 2004
Revised on August 19, 2004
Accepted on 27 August 2004

	Abstract

Proteasome-dependent proteolysis is essential for a number of key cellular processes and requires a sophisticated biogenesis pathway to function. Here, we have arrested the assembly process in its dynamic progression at the short-lived 16S state. Structural analysis of the 16S proteasome precursor intermediates by electron microscopy and single particle analysis reveals major conformational changes in the structure of the ring in comparison to a half of the 20S proteasome. The individual subunits in the 16S precursor complex rotate with respect to their positions in the X-ray crystallographic structure of the fully assembled 20S. This rearrangement results in a movement of the catalytic residue threonine 1 from the protected location in 16S precursor complexes to a more exposed position in the 20S structure. Thereby, our findings provide a molecular explanation for the structural rearrangements necessary for the dimerization of two 16S precursor complexes and the subsequent final maturation to active 20S proteasomes

Key Words: Docking, Electron microscopy, Proteasome biogenesis, Single particle analysis, Structural analysis