6BGL

Doubly PafE-capped 20S core particle in Mycobacterium tuberculosis

6BGL の概要

• エントリーDOI: 10.2210/pdb6bgl/pdb
• EMDBエントリー: 7097 7098
• 分子名称: Proteasome subunit alpha, Bacterial proteasome activator, Proteasome subunit beta (3 entities in total)
• 機能のキーワード: protein degradation, hydrolase
• 由来する生物種: Mycobacterium tuberculosis; 詳細
• 細胞内の位置: Cytoplasm : A5U4D5 A5U4D6
• タンパク質・核酸の鎖数: 42
• 化学式量合計: 996079.49

構造登録者

Li, H.,Hu, K. (登録日: 2017-10-28, 公開日: 2018-02-14, 最終更新日: 2024-03-13)

主引用文献

Hu, K.,Jastrab, J.B.,Zhang, S.,Kovach, A.,Zhao, G.,Darwin, K.H.,Li, H.
Proteasome substrate capture and gate opening by the accessory factor PafE fromMycobacterium tuberculosis.
J. Biol. Chem., 293:4713-4723, 2018

PubMed Abstract: In all domains of life, proteasomes are gated, chambered proteases that require opening by activators to facilitate protein degradation. Twelve proteasome accessory factor E (PafE) monomers assemble into a single dodecameric ring that promotes proteolysis required for the full virulence of the human bacterial pathogen Whereas the best characterized proteasome activators use ATP to deliver proteins into a proteasome, PafE does not require ATP. Here, to unravel the mechanism of PafE-mediated protein targeting and proteasome activation, we studied the interactions of PafE with native substrates, including a newly identified proteasome substrate, the ParA-like protein, Rv3213c, and with proteasome core particles. We characterized the function of a highly conserved feature in bacterial proteasome activator proteins: a glycine-glutamine-tyrosine-leucine (GQYL) motif at their C termini that is essential for stimulating proteolysis. Using cryo-electron microscopy (cryo-EM), we found that the GQYL motif of PafE interacts with specific residues in the α subunits of the proteasome core particle to trigger gate opening and degradation. Finally, we also found that PafE rings have 40-Å openings lined with hydrophobic residues that form a chamber for capturing substrates before they are degraded, suggesting PafE has a previously unrecognized chaperone activity. In summary, we have identified the interactions between PafE and the proteasome core particle that cause conformational changes leading to the opening of the proteasome gate and have uncovered a mechanism of PafE-mediated substrate degradation. Collectively, our results provide detailed insights into the mechanism of ATP-independent proteasome degradation in bacteria.

PubMed: 29414791
DOI: 10.1074/jbc.RA117.001471

実験手法

ELECTRON MICROSCOPY (3.4 Å)