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From Proteopedia
Singly PafE-capped 20S CP in Mycobacterium tuberculosis
Structural highlights
Function[PSA_MYCTA] Component of the proteasome core, a large protease complex with broad specificity involved in protein degradation. [BPA_MYCTO] Interacts with the core proteasome alpha-subunit (PrcA) through its C-terminal hydrophobic-tyrosine-X motif (HbYX motif). Interaction of Bpa with the proteasome stimulates proteosomal peptidase and casein degradation activity, which suggests Bpa could play a role in the removal of non-native or damaged proteins by influencing the conformation of the proteasome complex upon interaction. Can inhibit degradation of Pup-tagged substrates in vitro by competing with Mpa for association with the proteasome.[UniProtKB:P9WKX3] [PSB_MYCTA] Component of the proteasome core, a large protease complex with broad specificity involved in protein degradation. Publication Abstract from PubMedIn 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 Mycobacterium tuberculosis. 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 alpha subunits of the proteasome core particle to trigger gate opening and degradation. Finally, we also found that PafE rings have 40-A 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. Proteasome substrate capture and gate opening by the accessory factor PafE from Mycobacterium tuberculosis.,Hu K, Jastrab JB, Zhang S, Kovach A, Zhao G, Darwin KH, Li H J Biol Chem. 2018 Feb 5. pii: RA117.001471. doi: 10.1074/jbc.RA117.001471. PMID:29414791[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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