5lzp

From Proteopedia

(Difference between revisions)

Revision as of 10:57, 10 December 2016

Binding of the C-terminal GQYL motif of the bacterial proteasome activator Bpa to the 20S proteasome

Structural highlights

5lzp is a 35 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Activity:	Proteasome endopeptidase complex, with EC number 3.4.25.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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] [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.^[3] ^[4] [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.^[5]

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^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ 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
↑ Delley CL, Laederach J, Ziemski M, Bolten M, Boehringer D, Weber-Ban E. Bacterial proteasome activator bpa (rv3780) is a novel ring-shaped interactor of the mycobacterial proteasome. PLoS One. 2014 Dec 3;9(12):e114348. doi: 10.1371/journal.pone.0114348., eCollection 2014. PMID:25469515 doi:http://dx.doi.org/10.1371/journal.pone.0114348
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5lzp"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5lzp is ON HOLD  until Paper Publication
+==Binding of the C-terminal GQYL motif of the bacterial proteasome activator Bpa to the 20S proteasome==
+<StructureSection load='5lzp' size='340' side='right' caption='[[5lzp]], [[Resolution|resolution]] 3.45&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5lzp]] is a 35 chain structure. 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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LZP FirstGlance]. <br>
+</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'>[http://oca.weizmann.ac.il/oca-docs/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>
+== 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>
+<div style="background-color:#fffaf0;">
+== 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.
-Authors:
+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<ref>PMID:27839949</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5lzp" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Proteasome endopeptidase complex]]
+[[Category: Ban, N]]
+[[Category: Boehringer, D]]
+[[Category: Bolten, M]]
+[[Category: Delley, C L]]
+[[Category: Leibundgut, M]]
+[[Category: Weber-Ban, E]]
+[[Category: Complex]]
+[[Category: Hydrolase]]
+[[Category: Proteasome]]
+[[Category: Proteasome activator]]
+[[Category: Protein degradation]]

5lzp

From Proteopedia

Revision as of 10:57, 10 December 2016

Binding of the C-terminal GQYL motif of the bacterial proteasome activator Bpa to the 20S proteasome

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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