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| | <SX load='5lzp' size='340' side='right' viewer='molstar' caption='[[5lzp]], [[Resolution|resolution]] 3.45Å' scene=''> | | <SX load='5lzp' size='340' side='right' viewer='molstar' caption='[[5lzp]], [[Resolution|resolution]] 3.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5lzp]] is a 35 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LZP OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5LZP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5lzp]] is a 35 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LZP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LZP FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">prcA, Rv2109c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU]), bpa, Rv3780, MTCY13D12.14 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU]), prcB, Rv2110c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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]] 3.45Å</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=5lzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lzp OCA], [https://pdbe.org/5lzp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lzp RCSB], [https://www.ebi.ac.uk/pdbsum/5lzp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lzp ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5lzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lzp OCA], [http://pdbe.org/5lzp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lzp RCSB], [http://www.ebi.ac.uk/pdbsum/5lzp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lzp ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> [[http://www.uniprot.org/uniprot/PSB_MYCTU PSB_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> [[http://www.uniprot.org/uniprot/BPA_MYCTU BPA_MYCTU]] 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.<ref>PMID:25469515</ref> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </SX> | | </SX> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Myctu]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Proteasome endopeptidase complex]]
| + | [[Category: Ban N]] |
| - | [[Category: Ban, N]] | + | [[Category: Boehringer D]] |
| - | [[Category: Boehringer, D]] | + | [[Category: Bolten M]] |
| - | [[Category: Bolten, M]] | + | [[Category: Delley CL]] |
| - | [[Category: Delley, C L]] | + | [[Category: Leibundgut M]] |
| - | [[Category: Leibundgut, M]] | + | [[Category: Weber-Ban E]] |
| - | [[Category: Weber-Ban, E]] | + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Proteasome]]
| + | |
| - | [[Category: Proteasome activator]]
| + | |
| - | [[Category: Protein degradation]]
| + | |
| Structural highlights
Function
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.[1] [2]
Publication Abstract from PubMed
Mycobacterium tuberculosis harbors proteasomes that recruit substrates for degradation through an ubiquitin-like modification pathway. Recently, a non-ATPase activator termed Bpa (bacterial proteasome activator) was shown to support an alternate proteasomal degradation pathway. Here, we present the cryo-electron microscopy (cryo-EM) structure of Bpa in complex with the 20S core particle (CP). For docking into the cryo-EM density, we solved the X-ray structure of Bpa, showing that it forms tight four-helix bundles arranged into a 12-membered ring with a 40 A wide central pore and the C-terminal helix of each protomer protruding from the ring. The Bpa model was fitted into the cryo-EM map of the Bpa-CP complex, revealing its architecture and striking symmetry mismatch. The Bpa-CP interface was resolved to 3.5 A, showing the interactions between the C-terminal GQYL motif of Bpa and the proteasome alpha-rings. This docking mode is related to the one observed for eukaryotic activators with features specific to the bacterial complex.
Structural Analysis of the Bacterial Proteasome Activator Bpa in Complex with the 20S Proteasome.,Bolten M, Delley CL, Leibundgut M, Boehringer D, Ban N, Weber-Ban E Structure. 2016 Dec 6;24(12):2138-2151. doi: 10.1016/j.str.2016.10.008. Epub 2016, Nov 10. PMID:27839949[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lin G, Hu G, Tsu C, Kunes YZ, Li H, Dick L, Parsons T, Li P, Chen Z, Zwickl P, Weich N, Nathan C. Mycobacterium tuberculosis prcBA genes encode a gated proteasome with broad oligopeptide specificity. Mol Microbiol. 2006 Mar;59(5):1405-16. PMID:16468985 doi:http://dx.doi.org/10.1111/j.1365-2958.2005.05035.x
- ↑ Gandotra S, Schnappinger D, Monteleone M, Hillen W, Ehrt S. In vivo gene silencing identifies the Mycobacterium tuberculosis proteasome as essential for the bacteria to persist in mice. Nat Med. 2007 Dec;13(12):1515-20. Epub 2007 Dec 2. PMID:18059281 doi:http://dx.doi.org/10.1038/nm1683
- ↑ Bolten M, Delley CL, Leibundgut M, Boehringer D, Ban N, Weber-Ban E. Structural Analysis of the Bacterial Proteasome Activator Bpa in Complex with the 20S Proteasome. Structure. 2016 Dec 6;24(12):2138-2151. doi: 10.1016/j.str.2016.10.008. Epub 2016, Nov 10. PMID:27839949 doi:http://dx.doi.org/10.1016/j.str.2016.10.008
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