4cc4: Difference between revisions
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==Complex of InlC of Listeria monocytogenes and human Tuba C-terminal SH3 domain== | ==Complex of InlC of Listeria monocytogenes and human Tuba C-terminal SH3 domain== | ||
<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 [ | <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><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='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='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'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [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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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Ireton | [[Category: Listeria monocytogenes EGD-e]] | ||
[[Category: Julian | [[Category: Ireton K]] | ||
[[Category: Polle | [[Category: Julian R]] | ||
[[Category: Rigano | [[Category: Polle L]] | ||
[[Category: Schubert | [[Category: Rigano L]] | ||
[[Category: Schubert W-D]] | |||
Latest revision as of 15:07, 20 December 2023
Complex of InlC of Listeria monocytogenes and human Tuba C-terminal SH3 domainComplex of InlC of Listeria monocytogenes and human Tuba C-terminal SH3 domain
Structural highlights
FunctionINLC_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 PubMedThe 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
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