This Article Full Text Full Text (PDF) All Versions of this Article: biophysj.104.051144v1 biophysj.104.051144v2 87/6/4098    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mullapudi, S. Articles by Penczek, P. A. Search for Related Content PubMed PubMed Citation Articles by Mullapudi, S. Articles by Penczek, P. A.

Rearrangement of the 16S Precursor Subunits Is Essential for the Formation of the Active 20S Proteasome

Srinivas Mullapudi ^*, Lee Pullan ^*, Ozlem T. Bishop ^*, Hassan Khalil ^*, James K. Stoops , Roland Beckmann , Peter M. Kloetzel , Elke Krüger  and Pawel A. Penczek ^*

^* Department of Biochemistry and Molecular Biology, and Department of Pathology, The University of Texas-Houston Medical School, Houston, Texas 77030 USA; and Institut für Biochemie, Charité Universitaetsmedizin, 10117 Berlin, Germany

Correspondence: Address reprint requests to P. A. Penczek, E-mail: pawel.a.penczek{at}uth.tmc.edu.

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 ß-ring in comparison with one-half of the 20S proteasome. The individual ß-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.