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| | <StructureSection load='5x1e' size='340' side='right'caption='[[5x1e]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='5x1e' size='340' side='right'caption='[[5x1e]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5x1e]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X1E OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5X1E FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5x1e]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Legionella_pneumophila_subsp._pneumophila_str._Philadelphia_1 Legionella pneumophila subsp. pneumophila str. Philadelphia 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X1E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5X1E FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5x1h|5x1h]]</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]] 1.999Å</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=5x1e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x1e OCA], [http://pdbe.org/5x1e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x1e RCSB], [http://www.ebi.ac.uk/pdbsum/5x1e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x1e ProSAT]</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=5x1e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x1e OCA], [https://pdbe.org/5x1e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5x1e RCSB], [https://www.ebi.ac.uk/pdbsum/5x1e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5x1e ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/ICMS_LEGPH ICMS_LEGPH] Component of the Dot/Icm type IVB secretion system (T4BSS), which is used to inject bacterial effector proteins into eukaryotic host cells (PubMed:15661013, PubMed:18069892, PubMed:17040490, PubMed:22694730, PubMed:32513920). Part of a subcomplex which recruits effector proteins and delivers them to the core transmembrane subcomplex (PubMed:23028312, PubMed:32513920). The IcmS/IcmW protein complex plays an important role in protein translocation by interacting with multiple Dot/Icm effector proteins to facilitate their translocation into host cells (PubMed:15661013, PubMed:18069892). Interaction promotes conformational changes in the effector protein, which may facilitate display of a C-terminal translocation signal (PubMed:18069892). May maintain the substrates in a translocation competent form (PubMed:23028312). Required for intracellular growth in host cells, replicative phagosome formation and phagosome trafficking (PubMed:11115108). IcmS is required for IcmW stability (PubMed:15661013, PubMed:29203674).<ref>PMID:11115108</ref> <ref>PMID:15661013</ref> <ref>PMID:17040490</ref> <ref>PMID:18069892</ref> <ref>PMID:22694730</ref> <ref>PMID:23028312</ref> <ref>PMID:29203674</ref> <ref>PMID:32513920</ref> |
| - | Many bacteria, including Legionella pneumophila, rely on the type IV secretion system to translocate a repertoire of effector proteins into the hosts for their survival and growth. Type IV coupling protein (T4CP) is a hexameric ATPase that links translocating substrates to the transenvelope secretion conduit. Yet, how a large number of effector proteins are selectively recruited and processed by T4CPs remains enigmatic. DotL, the T4CP of L. pneumophila, contains an ATPase domain and a C-terminal extension whose function is unknown. Unlike T4CPs involved in plasmid DNA translocation, DotL appeared to function by forming a multiprotein complex with four other proteins. Here, we show that the C-terminal extension of DotL interacts with DotN, IcmS, IcmW and an additionally identified subunit LvgA, and that this pentameric assembly binds Legionella effector proteins. We determined the crystal structure of this assembly and built an architecture of the T4CP holocomplex by combining a homology model of the ATPase domain of DotL. The holocomplex is a hexamer of a bipartite structure composed of a membrane-proximal ATPase domain and a membrane-distal substrate-recognition assembly. The presented information demonstrates the architecture and functional dissection of the multiprotein T4CP complexes and provides important insights into their substrate recruitment and processing.
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| - | | + | |
| - | Architecture of the type IV coupling protein complex of Legionella pneumophila.,Kwak MJ, Kim JD, Kim H, Kim C, Bowman JW, Kim S, Joo K, Lee J, Jin KS, Kim YG, Lee NK, Jung JU, Oh BH Nat Microbiol. 2017 Jul 17;2:17114. doi: 10.1038/nmicrobiol.2017.114. PMID:28714967<ref>PMID:28714967</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div> | + | |
| - | <div class="pdbe-citations 5x1e" style="background-color:#fffaf0;"></div> | + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kim, J D]] | + | [[Category: Legionella pneumophila subsp. pneumophila str. Philadelphia 1]] |
| - | [[Category: Kwak, M J]] | + | [[Category: Kim JD]] |
| - | [[Category: Oh, B H]] | + | [[Category: Kwak MJ]] |
| - | [[Category: Coupling protein complex]] | + | [[Category: Oh BH]] |
| - | [[Category: Effector translocation]]
| + | |
| - | [[Category: Protein transport]]
| + | |
| - | [[Category: Type iv secretion system]]
| + | |
| Structural highlights
Function
ICMS_LEGPH Component of the Dot/Icm type IVB secretion system (T4BSS), which is used to inject bacterial effector proteins into eukaryotic host cells (PubMed:15661013, PubMed:18069892, PubMed:17040490, PubMed:22694730, PubMed:32513920). Part of a subcomplex which recruits effector proteins and delivers them to the core transmembrane subcomplex (PubMed:23028312, PubMed:32513920). The IcmS/IcmW protein complex plays an important role in protein translocation by interacting with multiple Dot/Icm effector proteins to facilitate their translocation into host cells (PubMed:15661013, PubMed:18069892). Interaction promotes conformational changes in the effector protein, which may facilitate display of a C-terminal translocation signal (PubMed:18069892). May maintain the substrates in a translocation competent form (PubMed:23028312). Required for intracellular growth in host cells, replicative phagosome formation and phagosome trafficking (PubMed:11115108). IcmS is required for IcmW stability (PubMed:15661013, PubMed:29203674).[1] [2] [3] [4] [5] [6] [7] [8]
References
- ↑ Coers J, Kagan JC, Matthews M, Nagai H, Zuckman DM, Roy CR. Identification of Icm protein complexes that play distinct roles in the biogenesis of an organelle permissive for Legionella pneumophila intracellular growth. Mol Microbiol. 2000 Nov;38(4):719-36. PMID:11115108 doi:10.1046/j.1365-2958.2000.02176.x
- ↑ Ninio S, Zuckman-Cholon DM, Cambronne ED, Roy CR. The Legionella IcmS-IcmW protein complex is important for Dot/Icm-mediated protein translocation. Mol Microbiol. 2005 Feb;55(3):912-26. PMID:15661013 doi:10.1111/j.1365-2958.2004.04435.x
- ↑ Vincent CD, Friedman JR, Jeong KC, Buford EC, Miller JL, Vogel JP. Identification of the core transmembrane complex of the Legionella Dot/Icm type IV secretion system. Mol Microbiol. 2006 Dec;62(5):1278-91. doi: 10.1111/j.1365-2958.2006.05446.x. , Epub 2006 Oct 16. PMID:17040490 doi:http://dx.doi.org/10.1111/j.1365-2958.2006.05446.x
- ↑ Cambronne ED, Roy CR. The Legionella pneumophila IcmSW complex interacts with multiple Dot/Icm effectors to facilitate type IV translocation. PLoS Pathog. 2007 Dec;3(12):e188. PMID:18069892 doi:10.1371/journal.ppat.0030188
- ↑ Vincent CD, Friedman JR, Jeong KC, Sutherland MC, Vogel JP. Identification of the DotL coupling protein subcomplex of the Legionella Dot/Icm type IV secretion system. Mol Microbiol. 2012 Jul;85(2):378-91. doi: 10.1111/j.1365-2958.2012.08118.x. Epub , 2012 Jun 14. PMID:22694730 doi:http://dx.doi.org/10.1111/j.1365-2958.2012.08118.x
- ↑ Sutherland MC, Nguyen TL, Tseng V, Vogel JP. The Legionella IcmSW complex directly interacts with DotL to mediate translocation of adaptor-dependent substrates. PLoS Pathog. 2012 Sep;8(9):e1002910. doi: 10.1371/journal.ppat.1002910. Epub 2012 , Sep 13. PMID:23028312 doi:http://dx.doi.org/10.1371/journal.ppat.1002910
- ↑ Xu J, Xu D, Wan M, Yin L, Wang X, Wu L, Liu Y, Liu X, Zhou Y, Zhu Y. Structural insights into the roles of the IcmS-IcmW complex in the type IVb secretion system of Legionella pneumophila. Proc Natl Acad Sci U S A. 2017 Dec 19;114(51):13543-13548. PMID:29203674 doi:10.1073/pnas.1706883115
- ↑ Meir A, Mace K, Lukoyanova N, Chetrit D, Hospenthal MK, Redzej A, Roy C, Waksman G. Mechanism of effector capture and delivery by the type IV secretion system from Legionella pneumophila. Nat Commun. 2020 Jun 8;11(1):2864. doi: 10.1038/s41467-020-16681-z. PMID:32513920 doi:http://dx.doi.org/10.1038/s41467-020-16681-z
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