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==Structure of PE5-PPE4-EspG3 complex from the type VII (ESX-3) secretion system, space group P212121==
<StructureSection load='6uuj' size='340' side='right'caption='[[6uuj]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6uuj]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_marinum_M Mycobacterium marinum M] and [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=6UUJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UUJ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</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=6uuj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uuj OCA], [https://pdbe.org/6uuj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uuj RCSB], [https://www.ebi.ac.uk/pdbsum/6uuj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uuj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PE05_MYCTU PE05_MYCTU] Important for the siderophore-mediated iron-acquisition function of ESX-3 (PubMed:26729876). May play a pivotal role in the evasion of host immune response by M.tuberculosis. Mediates production of IL-10 via activation of the p38 and ERK1/2 mitogen-activated protein kinase (MAPK) signaling pathways (PubMed:23284742).<ref>PMID:23284742</ref> <ref>PMID:26729876</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mycobacterium tuberculosis has evolved numerous type VII secretion (ESX) systems to secrete multiple factors important for both growth and virulence across their cell envelope. ESX-1, ESX-3, and ESX-5 systems have been shown to each secrete a distinct set of substrates, including PE and PPE families of proteins, named for conserved Pro-Glu and Pro-Pro-Glu motifs in their N termini. Proper secretion of the PE-PPE proteins requires the presence of EspG, with each system encoding its own unique copy. There is no cross-talk between any of the ESX systems, and how each EspG recognizes its subset of PE-PPE proteins is currently unknown. The only current structural characterization of PE-PPE-EspG heterotrimers is from the ESX-5 system. Here we present the crystal structure of the PE5mt-PPE4mt-EspG3mm heterotrimer from the ESX-3 system. Our heterotrimer reveals that EspG3mm interacts exclusively with PPE4mt in a similar manner to EspG5, shielding the hydrophobic tip of PPE4mt from solvent. The C-terminal helical domain of EspG3mm is dynamic, alternating between "open" and "closed" forms, and this movement is likely functionally relevant in the unloading of PE-PPE heterodimers at the secretion machinery. In contrast to the previously solved ESX-5 heterotrimers, the PE-PPE heterodimer of our ESX-3 heterotrimer is interacting with its chaperone at a drastically different angle and presents different faces of the PPE protein to the chaperone. We conclude that the PPE-EspG interface from each ESX system has a unique shape complementarity that allows each EspG to discriminate among noncognate PE-PPE pairs.

PE5-PPE4-EspG3 heterotrimer structure from mycobacterial ESX-3 secretion system gives insight into cognate substrate recognition by ESX systems.,Williamson ZA, Chaton CT, Ciocca WA, Korotkova N, Korotkov KV J Biol Chem. 2020 Sep 4;295(36):12706-12715. doi: 10.1074/jbc.RA120.012698. Epub , 2020 Jul 16. PMID:32675282<ref>PMID:32675282</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6uuj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium marinum M]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Korotkov KV]]
[[Category: Williamson ZA]]