Structural Analysis of the Bacterial Proteasome Activator Bpa in Complex with the 20S Proteasome

Structure. 2016 Dec 6;24(12):2138-2151. doi: 10.1016/j.str.2016.10.008. Epub 2016 Nov 10.

Abstract

Mycobacterium tuberculosis harbors proteasomes that recruit substrates for degradation through an ubiquitin-like modification pathway. Recently, a non-ATPase activator termed Bpa (bacterial proteasome activator) was shown to support an alternate proteasomal degradation pathway. Here, we present the cryo-electron microscopy (cryo-EM) structure of Bpa in complex with the 20S core particle (CP). For docking into the cryo-EM density, we solved the X-ray structure of Bpa, showing that it forms tight four-helix bundles arranged into a 12-membered ring with a 40 Å wide central pore and the C-terminal helix of each protomer protruding from the ring. The Bpa model was fitted into the cryo-EM map of the Bpa-CP complex, revealing its architecture and striking symmetry mismatch. The Bpa-CP interface was resolved to 3.5 Å, showing the interactions between the C-terminal GQYL motif of Bpa and the proteasome α-rings. This docking mode is related to the one observed for eukaryotic activators with features specific to the bacterial complex.

Keywords: Bpa; Mycobacterium tuberculosis; PafE; bacterial proteasome activator; degradation; proteasome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Cryoelectron Microscopy
  • Models, Molecular
  • Molecular Docking Simulation
  • Mycobacterium tuberculosis / chemistry
  • Mycobacterium tuberculosis / metabolism*
  • Proteasome Endopeptidase Complex / chemistry*
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Structure, Secondary

Substances

  • Bacterial Proteins
  • Proteasome Endopeptidase Complex