Structural basis for the assembly and gate closure mechanisms of the Mycobacterium tuberculosis 20S proteasome

Journal Article · Wed Jun 16 04:00:00 EDT 2010 · EMBO Journal

DOI:https://doi.org/10.1038/emboj.2010.95· OSTI ID:1040570

Li, D; Li, H; Li, H; Wang, T; Pan, H; Lin, G

Mycobacterium tuberculosis (Mtb) possesses a proteasome system analogous to the eukaryotic ubiquitin-proteasome pathway. Mtb requires the proteasome to resist killing by the host immune system. The detailed assembly process and the gating mechanism of Mtb proteasome have remained unknown. Using cryo-electron microscopy and X-ray crystallography, we have obtained structures of three Mtb proteasome assembly intermediates, showing conformational changes during assembly, and explaining why the {beta}-subunit propeptide inhibits rather than promotes assembly. Although the eukaryotic proteasome core particles close their protein substrate entrance gates with different amino terminal peptides of the seven {alpha}-subunits, it has been unknown how a prokaryotic proteasome might close the gate at the symmetry axis with seven identical peptides. We found in the new Mtb proteasome crystal structure that the gate is tightly sealed by the seven identical peptides taking on three distinct conformations. Our work provides the structural bases for assembly and gating mechanisms of the Mtb proteasome.

• Research Organization: BROOKHAVEN NATIONAL LABORATORY (BNL)
• Sponsoring Organization: NATIONAL INSTITUTE OF HEALTH
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 1040570
• Report Number(s): BNL--93652-2011-JA; 400412000
• Journal Information: EMBO Journal, Journal Name: EMBO Journal Journal Issue: 12 Vol. 29; ISSN EMJODG; ISSN 0261-4189
• Country of Publication: United States
• Language: English

Related Subjects

20S proteasome assembly
20S proteasome gating
59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
CONFORMATIONAL CHANGES
CRYSTAL STRUCTURE
CRYSTALLOGRAPHY
MICROSCOPY
MYCOBACTERIUM TUBERCULOSIS
Mycobacterium tuberculosis
PEPTIDES
PROTEINS
SUBSTRATES
SYMMETRY
X-ray crystallography
cryo-electron microscopy