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

Biophys J. 2004 Dec;87(6):4098-105. doi: 10.1529/biophysj.104.051144. Epub 2004 Sep 10.

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

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Computer Simulation
  • Crystallization / methods*
  • Crystallography / methods
  • Dimerization
  • Enzyme Activation
  • Image Interpretation, Computer-Assisted / methods
  • Models, Chemical*
  • Models, Molecular*
  • Multiprotein Complexes / chemistry
  • Proteasome Endopeptidase Complex / chemical synthesis*
  • Proteasome Endopeptidase Complex / ultrastructure*
  • Protein Conformation
  • Protein Subunits
  • RNA, Ribosomal, 16S / chemistry*
  • RNA, Ribosomal, 16S / ultrastructure*
  • Structure-Activity Relationship

Substances

  • Multiprotein Complexes
  • Protein Subunits
  • RNA, Ribosomal, 16S
  • Proteasome Endopeptidase Complex