6BGO
Singly PafE-capped 20S CP in Mycobacterium tuberculosis
Summary for 6BGO
| Entry DOI | 10.2210/pdb6bgo/pdb |
| EMDB information | 7097 7098 |
| Descriptor | Proteasome subunit alpha, Proteasome subunit beta, Bacterial proteasome activator (3 entities in total) |
| Functional Keywords | protein degradation, hydrolase |
| Biological source | Mycobacterium tuberculosis More |
| Cellular location | Cytoplasm : A5U4D5 A5U4D6 |
| Total number of polymer chains | 35 |
| Total formula weight | 863336.87 |
| Authors | |
| Primary citation | 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 Cited by 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: 29414791DOI: 10.1074/jbc.RA117.001471 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.2 Å) |
Structure validation
Download full validation report
