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| <SX load='6bgo' size='340' side='right' viewer='molstar' caption='[[6bgo]], [[Resolution|resolution]] 4.20Å' scene=''> | | <SX load='6bgo' size='340' side='right' viewer='molstar' caption='[[6bgo]], [[Resolution|resolution]] 4.20Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6bgo]] is a 35 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BGO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BGO FirstGlance]. <br> | | <table><tr><td colspan='2'>[[6bgo]] is a 35 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BGO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BGO FirstGlance]. <br> |
| </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">prcA, MRA_2124 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884]), prcB, MRA_2125 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884]), bpa, MT3889 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.2Å</td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Proteasome_endopeptidase_complex Proteasome endopeptidase complex], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.25.1 3.4.25.1] </span></td></tr>
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6bgo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bgo OCA], [https://pdbe.org/6bgo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bgo RCSB], [https://www.ebi.ac.uk/pdbsum/6bgo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bgo ProSAT]</span></td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6bgo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bgo OCA], [http://pdbe.org/6bgo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bgo RCSB], [http://www.ebi.ac.uk/pdbsum/6bgo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bgo ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/PSA_MYCTA PSA_MYCTA]] Component of the proteasome core, a large protease complex with broad specificity involved in protein degradation. [[http://www.uniprot.org/uniprot/BPA_MYCTO 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] [[http://www.uniprot.org/uniprot/PSB_MYCTA PSB_MYCTA]] Component of the proteasome core, a large protease complex with broad specificity involved in protein degradation. | | [https://www.uniprot.org/uniprot/PSA_MYCTU PSA_MYCTU] Component of the proteasome core, a large protease complex with broad specificity involved in protein degradation. The M.tuberculosis proteasome is able to cleave oligopeptides not only after hydrophobic but also after basic, acidic and small neutral residues. Among the identified substrates of the M.tuberculosis proteasome are the pupylated FabD, PanB and Mpa proteins. One function of the proteasome is to contribute to M.tuberculosis ability to resist killing by host macrophages, since the core proteasome is essential for persistence of the pathogen during the chronic phase of infection in mice. The mechanism of protection against bactericidal chemistries of the host's immune response probably involves the degradation of proteins that are irreversibly oxidized, nitrated, or nitrosated.<ref>PMID:16468985</ref> <ref>PMID:18059281</ref> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| 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 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.
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| 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<ref>PMID:29414791</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 6bgo" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
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| </SX> | | </SX> |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Proteasome endopeptidase complex]] | | [[Category: Mycobacterium tuberculosis]] |
| [[Category: Hu, K]] | | [[Category: Hu K]] |
| [[Category: Li, H]] | | [[Category: Li H]] |
| [[Category: Hydrolase]]
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| [[Category: Protein degradation]]
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