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2lnh

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Revision as of 19:25, 1 August 2018

Enterohaemorrhagic E. coli (EHEC) exploits a tryptophan switch to hijack host F-actin assembly

Structural highlights

2lnh is a 3 chain structure with sequence from Eco57 and Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	WASL (HUMAN), BAIAP2L1, IRTKS (HUMAN), espF(U), tccP (ECO57)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[WASL_HUMAN] Regulates actin polymerization by stimulating the actin-nucleating activity of the Arp2/3 complex. Binds to HSF1/HSTF1 and forms a complex on heat shock promoter elements (HSE) that negatively regulates HSP90 expression.^[1] [ESFU3_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.^[2] ^[3] [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.^[4] ^[5] ^[6]

Publication Abstract from PubMed

Intrinsically disordered protein (IDP)-mediated interactions are often characterized by low affinity but high specificity. These traits are essential in signaling and regulation that require reversibility. Enterohaemorrhagic Escherichia coli (EHEC) exploit this situation by commandeering host cytoskeletal signaling to stimulate actin assembly beneath bound bacteria, generating "pedestals" that promote intestinal colonization. EHEC translocates two proteins, EspF(U) and Tir, which form a complex with the host protein IRTKS. The interaction of this complex with N-WASP triggers localized actin polymerization. We show that EspF(U) is an IDP that contains a transiently alpha-helical N-terminus and dynamic C-terminus. Our structure shows that single EspF(U) repeat forms a high-affinity trimolecular complex with N-WASP and IRTKS. We demonstrate that bacterial and cellular ligands interact with IRTKS SH3 in a similar fashion, but the bacterial protein has evolved to outcompete cellular targets by utilizing a tryptophan switch that offers superior binding affinity enabling EHEC-induced pedestal formation.

Enterohaemorrhagic Escherichia Coli Exploits a Tryptophan Switch to Hijack Host F-Actin Assembly.,Aitio O, Hellman M, Skehan B, Kesti T, Leong JM, Saksela K, Permi P Structure. 2012 Aug 21. PMID:22921828^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Vingadassalom D, Kazlauskas A, Skehan B, Cheng HC, Magoun L, Robbins D, Rosen MK, Saksela K, Leong JM. Insulin receptor tyrosine kinase substrate links the E. coli O157:H7 actin assembly effectors Tir and EspF(U) during pedestal formation. Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6754-9. doi:, 10.1073/pnas.0809131106. Epub 2009 Apr 6. PMID:19366662 doi:10.1073/pnas.0809131106
↑ Cheng HC, Skehan BM, Campellone KG, Leong JM, Rosen MK. Structural mechanism of WASP activation by the enterohaemorrhagic E. coli effector EspF(U). Nature. 2008 Aug 21;454(7207):1009-13. Epub 2008 Jul 23. PMID:18650809 doi:10.1038/nature07160
↑ Aitio O, Hellman M, Skehan B, Kesti T, Leong JM, Saksela K, Permi P. Enterohaemorrhagic Escherichia Coli Exploits a Tryptophan Switch to Hijack Host F-Actin Assembly. Structure. 2012 Aug 21. PMID:22921828 doi:http://dx.doi.org/10.1016/j.str.2012.07.015
↑ Millard TH, Dawson J, Machesky LM. Characterisation of IRTKS, a novel IRSp53/MIM family actin regulator with distinct filament bundling properties. J Cell Sci. 2007 May 1;120(Pt 9):1663-72. Epub 2007 Apr 12. PMID:17430976 doi:http://dx.doi.org/jcs.001776
↑ Vingadassalom D, Kazlauskas A, Skehan B, Cheng HC, Magoun L, Robbins D, Rosen MK, Saksela K, Leong JM. Insulin receptor tyrosine kinase substrate links the E. coli O157:H7 actin assembly effectors Tir and EspF(U) during pedestal formation. Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6754-9. doi:, 10.1073/pnas.0809131106. Epub 2009 Apr 6. PMID:19366662 doi:10.1073/pnas.0809131106
↑ Aitio O, Hellman M, Skehan B, Kesti T, Leong JM, Saksela K, Permi P. Enterohaemorrhagic Escherichia Coli Exploits a Tryptophan Switch to Hijack Host F-Actin Assembly. Structure. 2012 Aug 21. PMID:22921828 doi:http://dx.doi.org/10.1016/j.str.2012.07.015
↑ Aitio O, Hellman M, Skehan B, Kesti T, Leong JM, Saksela K, Permi P. Enterohaemorrhagic Escherichia Coli Exploits a Tryptophan Switch to Hijack Host F-Actin Assembly. Structure. 2012 Aug 21. PMID:22921828 doi:http://dx.doi.org/10.1016/j.str.2012.07.015

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2lnh"

@@ Line 1: / Line 1: @@
 ==Enterohaemorrhagic E. coli (EHEC) exploits a tryptophan switch to hijack host F-actin assembly==
 <StructureSection load='2lnh' size='340' side='right' caption='[[2lnh]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[2lnh]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Eco57 Eco57] and [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LNH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LNH FirstGlance]. <br>
 </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">WASL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), BAIAP2L1, IRTKS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), espF(U), tccP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83334 ECO57])</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=2lnh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lnh OCA], [http://pdbe.org/2lnh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2lnh RCSB], [http://www.ebi.ac.uk/pdbsum/2lnh PDBsum]</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=2lnh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lnh OCA], [http://pdbe.org/2lnh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2lnh RCSB], [http://www.ebi.ac.uk/pdbsum/2lnh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2lnh ProSAT]</span></td></tr>
 </table>
 == Function ==

2lnh

From Proteopedia

Revision as of 19:25, 1 August 2018

Enterohaemorrhagic E. coli (EHEC) exploits a tryptophan switch to hijack host F-actin assembly

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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