5wez

Structural highlights

Function

[CEST_ECO27] Chaperone for the type III secretion of Tir. Probably stabilizes the protein, prevents inappropriate protein-proteininteractions and aids in secretion. [TIR_ECO27] Multifunctional protein that is required for efficient pedestal formation in host epithelial cells during infection. The extracellular region acts as a receptor for bacterial intimin, allowing the bacterium to attach tightly to the host-cell surface. Simultaneously, the intracellular region initiates a signaling cascade in the host cell, which leads to actin polymerization and formation of actin pedestals at the sites of bacterial adhesion. In strain E2348/69, acts mainly via the host adaptor proteins NCK1 and NCK2. Once clustered and phosphorylated at Tyr-474, Tir binds to NCK proteins, which in turn bind and activate host WASL/N-WASP, leading to actin polymerization. Can also trigger an inefficient, NCK-independent pedestal formation. This pathway involves phosphorylation of Tyr-454 and probably a putative host adaptor. Acts also via direct binding to the host cytoskeletal protein alpha-actinin in a NCK- and phosphotyrosine-independent manner. This interaction may stabilize the pedestal, but is not essential for its formation.^{[1] [2] [3] [4] [5] [6]}

References

1. ↑ Kenny B. Phosphorylation of tyrosine 474 of the enteropathogenic Escherichia coli (EPEC) Tir receptor molecule is essential for actin nucleating activity and is preceded by additional host modifications. Mol Microbiol. 1999 Feb;31(4):1229-41. PMID:10096089
2. ↑ Campellone KG, Rankin S, Pawson T, Kirschner MW, Tipper DJ, Leong JM. Clustering of Nck by a 12-residue Tir phosphopeptide is sufficient to trigger localized actin assembly. J Cell Biol. 2004 Feb 2;164(3):407-16. PMID:14757753 doi:http://dx.doi.org/10.1083/jcb.200306032
3. ↑ Lommel S, Benesch S, Rohde M, Wehland J, Rottner K. Enterohaemorrhagic and enteropathogenic Escherichia coli use different mechanisms for actin pedestal formation that converge on N-WASP. Cell Microbiol. 2004 Mar;6(3):243-54. PMID:14764108
4. ↑ Campellone KG, Leong JM. Nck-independent actin assembly is mediated by two phosphorylated tyrosines within enteropathogenic Escherichia coli Tir. Mol Microbiol. 2005 Apr;56(2):416-32. PMID:15813734 doi:http://dx.doi.org/10.1111/j.1365-2958.2005.04548.x
5. ↑ Brady MJ, Campellone KG, Ghildiyal M, Leong JM. Enterohaemorrhagic and enteropathogenic Escherichia coli Tir proteins trigger a common Nck-independent actin assembly pathway. Cell Microbiol. 2007 Sep;9(9):2242-53. Epub 2007 May 23. PMID:17521329 doi:http://dx.doi.org/10.1111/j.1462-5822.2007.00954.x
6. ↑ Kenny B, DeVinney R, Stein M, Reinscheid DJ, Frey EA, Finlay BB. Enteropathogenic E. coli (EPEC) transfers its receptor for intimate adherence into mammalian cells. Cell. 1997 Nov 14;91(4):511-20. PMID:9390560