title: Structural Analysis of the Bacterial Proteasome Activator Bpa in Complex with the 20S Proteasome.
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.
authors.affiliation: ETH Zurich, Institute of Molecular Biology & Biophysics, 8093 Zurich, Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Bolten
authors.affiliation: ETH Zurich, Institute of Molecular Biology & Biophysics, 8093 Zurich, Switzerland.
authors.forename: Cyrille L
authors.initials: CL
authors.lastname: Delley
authors.affiliation: ETH Zurich, Institute of Molecular Biology & Biophysics, 8093 Zurich, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Leibundgut
authors.affiliation: ETH Zurich, Institute of Molecular Biology & Biophysics, 8093 Zurich, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Boehringer
authors.affiliation: ETH Zurich, Institute of Molecular Biology & Biophysics, 8093 Zurich, Switzerland.
authors.forename: Nenad
authors.initials: N
authors.lastname: Ban
authors.affiliation: ETH Zurich, Institute of Molecular Biology & Biophysics, 8093 Zurich, Switzerland. Electronic address: eilika@mol.biol.ethz.ch.
authors.forename: Eilika
authors.initials: E
authors.lastname: Weber-Ban
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D020285:Cryoelectron Microscopy; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry* / Q000378:metabolism*; D017433:Protein Structure, Secondary
chemical_list: D001426:Bacterial Proteins; D046988:Proteasome Endopeptidase Complex
keywords: Bpa; Mycobacterium tuberculosis; PafE; bacterial proteasome activator; degradation; proteasome