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TitleStructural Analysis of the Bacterial Proteasome Activator Bpa in Complex with the 20S Proteasome.
Journal, issue, pagesStructure, Vol. 24, Issue 12, Page 2138-2151, Year 2016
Publish dateDec 6, 2016
AuthorsMarcel Bolten / Cyrille L Delley / Marc Leibundgut / Daniel Boehringer / Nenad Ban / Eilika Weber-Ban /
PubMed AbstractMycobacterium tuberculosis harbors proteasomes that recruit substrates for degradation through an ubiquitin-like modification pathway. Recently, a non-ATPase activator termed Bpa (bacterial ...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.
External linksStructure / PubMed:27839949
MethodsEM (single particle) / X-ray diffraction
Resolution2.6 - 4.6 Å
Structure data

EMDB-4127:
Cryo-EM reconstruction of the Bacterial proteasome interactor (Bpa) bound to the 20S proteasome of M. tuberculosis.
Method: EM (single particle) / Resolution: 4.6 Å

EMDB-4128, PDB-5lzp:
Binding of the C-terminal GQYL motif of the bacterial proteasome activator Bpa to the 20S proteasome
Method: EM (single particle) / Resolution: 3.5 Å

PDB-5lfj:
Crystal Structure of the Bacterial Proteasome Activator Bpa of Mycobacterium tuberculosis
Method: X-RAY DIFFRACTION / Resolution: 2.6 Å

PDB-5lfp:
Crystal Structure of the Bacterial Proteasome Activator Bpa of Mycobacterium tuberculosis (space group P6322, SeMet)
Method: X-RAY DIFFRACTION / Resolution: 3.303 Å

PDB-5lfq:
Crystal Structure of the Bacterial Proteasome Activator Bpa of Mycobacterium tuberculosis (space group P3)
Method: X-RAY DIFFRACTION / Resolution: 3.503 Å

Chemicals

ChemComp-HOH:
WATER / Water

Source
  • mycobacterium tuberculosis h37rv (bacteria)
  • mycobacterium tuberculosis (strain atcc 25618 / h37rv) (bacteria)
KeywordsCHAPERONE / Dodecamer / four-helix bundle / SIGNALING PROTEIN / HYDROLASE / Proteasome / Proteasome activator / protein degradation / complex

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