View source for 7pxd


==Substrate-engaged mycobacterial Proteasome-associated ATPase in complex with open-gate 20S CP - composite map (state B)==
<StructureSection load='7pxd' size='340' side='right'caption='[[7pxd]], [[Resolution|resolution]] 4.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7pxd]] is a 36 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=7PXD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PXD FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=7pxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pxd OCA], [https://pdbe.org/7pxd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pxd RCSB], [https://www.ebi.ac.uk/pdbsum/7pxd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pxd ProSAT]</span></td></tr>
</table>
== Function ==
[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> 
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== Publication Abstract from PubMed ==
Proteasomes are present in eukaryotes, archaea and Actinobacteria, including the human pathogen Mycobacterium tuberculosis, where proteasomal degradation supports persistence inside the host. In mycobacteria and other members of Actinobacteria, prokaryotic ubiquitin-like protein (Pup) serves as a degradation tag post-translationally conjugated to target proteins for their recruitment to the mycobacterial proteasome ATPase (Mpa). Here, we use single-particle cryo-electron microscopy to determine the structure of Mpa in complex with the 20S core particle at an early stage of pupylated substrate recruitment, shedding light on the mechanism of substrate translocation. Two conformational states of Mpa show how substrate is translocated stepwise towards the degradation chamber of the proteasome core particle. We also demonstrate, in vitro and in vivo, the importance of a structural feature in Mpa that allows formation of alternating charge-complementary interactions with the proteasome resulting in radial, rail-guided movements during the ATPase conformational cycle.

Structural basis of prokaryotic ubiquitin-like protein engagement and translocation by the mycobacterial Mpa-proteasome complex.,Kavalchuk M, Jomaa A, Muller AU, Weber-Ban E Nat Commun. 2022 Jan 12;13(1):276. doi: 10.1038/s41467-021-27787-3. PMID:35022401<ref>PMID:35022401</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7pxd" style="background-color:#fffaf0;"></div>

==See Also==
*[[Proteasome 3D structures|Proteasome 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Jomaa A]]
[[Category: Kavalchuk M]]
[[Category: Weber-Ban E]]