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| | ==1H, 13C, and 15N Chemical Shift Assignments for IRTKS-SH3 and EspFu-R47 complex== | | ==1H, 13C, and 15N Chemical Shift Assignments for IRTKS-SH3 and EspFu-R47 complex== |
| - | <StructureSection load='2kxc' size='340' side='right' caption='[[2kxc]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2kxc' size='340' side='right'caption='[[2kxc]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2kxc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KXC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KXC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2kxc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_O157:H7 Escherichia coli O157:H7] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KXC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KXC FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BAIAP2L1, IRTKS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2kxc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kxc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2kxc RCSB], [http://www.ebi.ac.uk/pdbsum/2kxc PDBsum]</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=2kxc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kxc OCA], [https://pdbe.org/2kxc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kxc RCSB], [https://www.ebi.ac.uk/pdbsum/2kxc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kxc ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BI2L1_HUMAN BI2L1_HUMAN]] May function as adapter protein. Involved in the formation of clusters of actin bundles. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection.<ref>PMID:17430976</ref> <ref>PMID:19366662</ref> <ref>PMID:22921828</ref> [[http://www.uniprot.org/uniprot/Q8X2D5_ECO57 Q8X2D5_ECO57]] Required for efficient pedestal formation in host epithelial cells during infection. Acts as an intermediate between Tir (via host BAIAP2) and host WASL/N-WASP. Directly binds and activates WASL/N-WASP, which stimulates actin polymerization and leads to the formation of actin pedestals at the sites of bacterial adhesion (By similarity). | + | [https://www.uniprot.org/uniprot/BI2L1_HUMAN BI2L1_HUMAN] May function as adapter protein. Involved in the formation of clusters of actin bundles. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection.<ref>PMID:17430976</ref> <ref>PMID:19366662</ref> <ref>PMID:22921828</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Src homology 3 (SH3) domains are globular protein interaction modules that regulate cell behavior. The classic SH3 ligand-binding site accommodates a hydrophobic PxxP motif and a positively charged specificity-determining residue. We have determined the NMR structure of insulin receptor tyrosine kinase substrate (IRTKS) SH3 domain in complex with a repeat from Escherichia coli-secreted protein F-like protein encoded on prophage U (EspF(U)), a translocated effector of enterohemorrhagic E. coli that commandeers the mammalian actin assembly machinery. EspF(U)-IRTKS interaction is among the highest affinity natural SH3 ligands. Our complex structure reveals a unique type of SH3 interaction based on recognition of tandem PxxP motifs in the ligand. Strikingly, the specificity pocket of IRTKS SH3 has evolved to accommodate a polyproline type II helical peptide analogously to docking of the canonical PxxP by the conserved IRTKS SH3 proline-binding pockets. This cooperative binding explains the high-affinity SH3 interaction and is required for EspF(U)-IRTKS interaction in mammalian cells as well as the formation of localized actin "pedestals" beneath bound bacteria. Importantly, tandem PxxP motifs are also found in mammalian ligands and have been shown to contribute to IRTKS SH3 recognition similarly.
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| - | Recognition of tandem PxxP motifs as a unique Src homology 3-binding mode triggers pathogen-driven actin assembly.,Aitio O, Hellman M, Kazlauskas A, Vingadassalom DF, Leong JM, Saksela K, Permi P Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21743-8. Epub 2010 Nov 22. PMID:21098279<ref>PMID:21098279</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Escherichia coli]] | + | [[Category: Escherichia coli O157:H7]] |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Aitio, O]] | + | [[Category: Large Structures]] |
| - | [[Category: Hellman, M]] | + | [[Category: Aitio O]] |
| - | [[Category: Kazlauskas, A]] | + | [[Category: Hellman M]] |
| - | [[Category: Leong, J M]] | + | [[Category: Kazlauskas A]] |
| - | [[Category: Permi, P]] | + | [[Category: Leong JM]] |
| - | [[Category: Saksela, K]] | + | [[Category: Permi P]] |
| - | [[Category: Vingadassalom, D F]] | + | [[Category: Saksela K]] |
| - | [[Category: Complex structure]]
| + | [[Category: Vingadassalom DF]] |
| - | [[Category: Espfu]]
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| - | [[Category: Irtks-sh3]]
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| - | [[Category: Protein binding]]
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