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| | <StructureSection load='6vhr' size='340' side='right'caption='[[6vhr]], [[Resolution|resolution]] 3.30Å' scene=''> | | <StructureSection load='6vhr' size='340' side='right'caption='[[6vhr]], [[Resolution|resolution]] 3.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6vhr]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycmm Mycmm] and [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VHR OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VHR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6vhr]] is a 3 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=6VHR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VHR FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6uuj|6uuj]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PE5, Rv0285, LH57_01560 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU]), PPE4, Rv0286 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU]), MMAR_0548 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=216594 MYCMM])</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=6vhr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vhr OCA], [https://pdbe.org/6vhr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vhr RCSB], [https://www.ebi.ac.uk/pdbsum/6vhr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vhr 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=6vhr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vhr OCA], [http://pdbe.org/6vhr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vhr RCSB], [http://www.ebi.ac.uk/pdbsum/6vhr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vhr ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> [[http://www.uniprot.org/uniprot/PPE04_MYCTU PPE04_MYCTU]] Important for the siderophore-mediated iron-acquisition function of ESX-3.<ref>PMID:26729876</ref> | + | [https://www.uniprot.org/uniprot/PPE04_MYCTU PPE04_MYCTU] Important for the siderophore-mediated iron-acquisition function of ESX-3.<ref>PMID:26729876</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Mycmm]] | + | [[Category: Mycobacterium marinum M]] |
| - | [[Category: Myctu]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Korotkov, K V]] | + | [[Category: Korotkov KV]] |
| - | [[Category: Williamson, Z A]] | + | [[Category: Williamson ZA]] |
| - | [[Category: Chaperone]]
| + | |
| - | [[Category: Protein secretion]]
| + | |
| - | [[Category: Protein transport]]
| + | |
| Structural highlights
Function
PPE04_MYCTU Important for the siderophore-mediated iron-acquisition function of ESX-3.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tufariello JM, Chapman JR, Kerantzas CA, Wong KW, Vilcheze C, Jones CM, Cole LE, Tinaztepe E, Thompson V, Fenyo D, Niederweis M, Ueberheide B, Philips JA, Jacobs WR Jr. Separable roles for Mycobacterium tuberculosis ESX-3 effectors in iron acquisition and virulence. Proc Natl Acad Sci U S A. 2016 Jan 19;113(3):E348-57. doi:, 10.1073/pnas.1523321113. Epub 2016 Jan 4. PMID:26729876 doi:http://dx.doi.org/10.1073/pnas.1523321113
- ↑ Williamson ZA, Chaton CT, Ciocca WA, Korotkova N, Korotkov KV. PE5-PPE4-EspG3 heterotrimer structure from mycobacterial ESX-3 secretion system gives insight into cognate substrate recognition by ESX systems. J Biol Chem. 2020 Sep 4;295(36):12706-12715. doi: 10.1074/jbc.RA120.012698. Epub , 2020 Jul 16. PMID:32675282 doi:http://dx.doi.org/10.1074/jbc.RA120.012698
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