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| | <StructureSection load='4cc4' size='340' side='right'caption='[[4cc4]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='4cc4' size='340' side='right'caption='[[4cc4]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4cc4]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lismo Lismo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CC4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CC4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4cc4]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Listeria_monocytogenes_EGD-e Listeria monocytogenes EGD-e]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CC4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CC4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 2.6Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cc2|4cc2]], [[4cc3|4cc3]]</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=4cc4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cc4 OCA], [https://pdbe.org/4cc4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cc4 RCSB], [https://www.ebi.ac.uk/pdbsum/4cc4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cc4 ProSAT]</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=4cc4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cc4 OCA], [http://pdbe.org/4cc4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cc4 RCSB], [http://www.ebi.ac.uk/pdbsum/4cc4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cc4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DNMBP_HUMAN DNMBP_HUMAN]] Scaffold protein that links dynamin with actin-regulating proteins. May play a role in membrane trafficking between the cell surface and the Golgi (By similarity). | + | [https://www.uniprot.org/uniprot/INLC_LISMG INLC_LISMG] A virulence enhancer that has at least 2 dissociable functions in infection; it impairs translocation of host transcription factor NF-kappa-B to the nucleus and antagonizes the function of the Tuba dynamin-binding protein, promoting bacterial spreading (PubMed:20855622, PubMed:19767742, PubMed:24332715). Perturbs the morphology of host cell junctions by impairing host DNMBP (Tuba) and WASL interaction, altering cortical tension at the cell junctions and allowing bacteria to more efficiently form bacteria-filled cell protrusions which promote bacterial spreading within infected host tissue (PubMed:19767742, PubMed:24332715). Down-regulates the host inflammation response usually induced by Listeria infection. Interacts with host I-kappa-B kinase alpha (IKKA, CHUK), which prevents IKKA from phosphorylating NF-kappa-B inhibitor alpha (IKBA, NFKBIA) and thus delays degradation of phospho-IKBA. Translocation of host transcription factor p65 (a subunit of NF-kappa-B, RELA) into the nucleus is impaired, which prevents activation of NF-KB-regulated genes (PubMed:20855622). Recognized by serum from healthy humans exposed to L.monocytogenes as well from patients who have recovered from listeriosis (PubMed:9284184).<ref>PMID:19767742</ref> <ref>PMID:20855622</ref> <ref>PMID:24332715</ref> <ref>PMID:9284184</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4cc4" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4cc4" style="background-color:#fffaf0;"></div> |
| - | | |
| - | ==See Also== | |
| - | *[[Tuba 3D structures|Tuba 3D structures]] | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lismo]] | + | [[Category: Listeria monocytogenes EGD-e]] |
| - | [[Category: Ireton, K]] | + | [[Category: Ireton K]] |
| - | [[Category: Julian, R]] | + | [[Category: Julian R]] |
| - | [[Category: Polle, L]] | + | [[Category: Polle L]] |
| - | [[Category: Rigano, L]] | + | [[Category: Rigano L]] |
| - | [[Category: Schubert, W D]] | + | [[Category: Schubert W-D]] |
| - | [[Category: Bacterial infection]]
| + | |
| - | [[Category: Cell invasion]]
| + | |
| - | [[Category: Cell membrane protrusion]]
| + | |
| - | [[Category: Disruption of cortical tension]]
| + | |
| - | [[Category: Leucine-rich repeat]]
| + | |
| - | [[Category: Listerial cell-cell spread]]
| + | |
| - | [[Category: Pathogenesis]]
| + | |
| - | [[Category: Protein-protein interaction]]
| + | |
| - | [[Category: Src homology 3 domain]]
| + | |
| - | [[Category: Virulence factor]]
| + | |
| Structural highlights
4cc4 is a 6 chain structure with sequence from Homo sapiens and Listeria monocytogenes EGD-e. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.6Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
INLC_LISMG A virulence enhancer that has at least 2 dissociable functions in infection; it impairs translocation of host transcription factor NF-kappa-B to the nucleus and antagonizes the function of the Tuba dynamin-binding protein, promoting bacterial spreading (PubMed:20855622, PubMed:19767742, PubMed:24332715). Perturbs the morphology of host cell junctions by impairing host DNMBP (Tuba) and WASL interaction, altering cortical tension at the cell junctions and allowing bacteria to more efficiently form bacteria-filled cell protrusions which promote bacterial spreading within infected host tissue (PubMed:19767742, PubMed:24332715). Down-regulates the host inflammation response usually induced by Listeria infection. Interacts with host I-kappa-B kinase alpha (IKKA, CHUK), which prevents IKKA from phosphorylating NF-kappa-B inhibitor alpha (IKBA, NFKBIA) and thus delays degradation of phospho-IKBA. Translocation of host transcription factor p65 (a subunit of NF-kappa-B, RELA) into the nucleus is impaired, which prevents activation of NF-KB-regulated genes (PubMed:20855622). Recognized by serum from healthy humans exposed to L.monocytogenes as well from patients who have recovered from listeriosis (PubMed:9284184).[1] [2] [3] [4]
Publication Abstract from PubMed
The human pathogen Listeria monocytogenes is able to directly spread to neighboring cells of host tissues, a process recently linked to the virulence factor InlC. InlC targets the sixth SH3 domain (SH3-6) of human Tuba, disrupting its physiological interaction with the cytoskeletal protein N-WASP. The resulting loss of cortical actin tension may slacken the junctional membrane, allowing protrusion formation by motile Listeria. Complexes of Tuba SH3-6 with physiological partners N-WASP and Mena reveal equivalent binding modes but distinct affinities. The interaction surface of the infection complex InlC/Tuba SH3-6 is centered on phenylalanine 146 of InlC stacking upon asparagine 1569 of Tuba. Replacing Phe146 by alanine largely abrogates molecular affinity and in vivo mimics deletion of inlC. Collectively, our findings indicate that InlC hijacks Tuba through its LRR domain, blocking the peptide binding groove to prevent recruitment of its physiological partners.
Structural Details of Human Tuba Recruitment by InlC of Listeria monocytogenes Elucidate Bacterial Cell-Cell Spreading.,Polle L, Rigano LA, Julian R, Ireton K, Schubert WD Structure. 2013 Dec 10. pii: S0969-2126(13)00429-2. doi:, 10.1016/j.str.2013.10.017. PMID:24332715[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rajabian T, Gavicherla B, Heisig M, Muller-Altrock S, Goebel W, Gray-Owen SD, Ireton K. The bacterial virulence factor InlC perturbs apical cell junctions and promotes cell-to-cell spread of Listeria. Nat Cell Biol. 2009 Oct;11(10):1212-8. doi: 10.1038/ncb1964. Epub 2009 Sep 20. PMID:19767742 doi:http://dx.doi.org/10.1038/ncb1964
- ↑ Gouin E, Adib-Conquy M, Balestrino D, Nahori MA, Villiers V, Colland F, Dramsi S, Dussurget O, Cossart P. The Listeria monocytogenes InlC protein interferes with innate immune responses by targeting the I{kappa}B kinase subunit IKK{alpha}. Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17333-8. doi:, 10.1073/pnas.1007765107. Epub 2010 Sep 20. PMID:20855622 doi:http://dx.doi.org/10.1073/pnas.1007765107
- ↑ Polle L, Rigano LA, Julian R, Ireton K, Schubert WD. Structural Details of Human Tuba Recruitment by InlC of Listeria monocytogenes Elucidate Bacterial Cell-Cell Spreading. Structure. 2013 Dec 10. pii: S0969-2126(13)00429-2. doi:, 10.1016/j.str.2013.10.017. PMID:24332715 doi:http://dx.doi.org/10.1016/j.str.2013.10.017
- ↑ Grenningloh R, Darji A, Wehland J, Chakraborty T, Weiss S. Listeriolysin and IrpA are major protein targets of the human humoral response against Listeria monocytogenes. Infect Immun. 1997 Sep;65(9):3976-80. doi: 10.1128/iai.65.9.3976-3980.1997. PMID:9284184 doi:http://dx.doi.org/10.1128/iai.65.9.3976-3980.1997
- ↑ Polle L, Rigano LA, Julian R, Ireton K, Schubert WD. Structural Details of Human Tuba Recruitment by InlC of Listeria monocytogenes Elucidate Bacterial Cell-Cell Spreading. Structure. 2013 Dec 10. pii: S0969-2126(13)00429-2. doi:, 10.1016/j.str.2013.10.017. PMID:24332715 doi:http://dx.doi.org/10.1016/j.str.2013.10.017
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