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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 20 1692-703 (2012)
Cited: 21 times
EuropePMC logo PMID: 22921828

Abstract

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 α-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.

Reviews - 2lnh mentioned but not cited (1)

  1. Interesting Biochemistries in the Structure and Function of Bacterial Effectors. Mak H, Thurston TLM. Front Cell Infect Microbiol 11 608860 (2021)


Reviews citing this publication (5)

  1. The most important thing is the tail: multitudinous functionalities of intrinsically disordered protein termini. Uversky VN. FEBS Lett. 587 1891-1901 (2013)
  2. Intimate host attachment: enteropathogenic and enterohaemorrhagic Escherichia coli. Lai Y, Rosenshine I, Leong JM, Frankel G. Cell. Microbiol. 15 1796-1808 (2013)
  3. How pathogens use linear motifs to perturb host cell networks. Via A, Uyar B, Brun C, Zanzoni A. Trends Biochem. Sci. 40 36-48 (2015)
  4. Convergent evolution and mimicry of protein linear motifs in host-pathogen interactions. Chemes LB, de Prat-Gay G, Sánchez IE. Curr. Opin. Struct. Biol. 32 91-101 (2015)
  5. Structural features and interfacial properties of WH2, β-thymosin domains and other intrinsically disordered domains in the regulation of actin cytoskeleton dynamics. Renault L, Deville C, van Heijenoort C. Cytoskeleton (Hoboken) 70 686-705 (2013)

Articles citing this publication (15)

  1. Insulin receptor tyrosine kinase substrate activates EGFR/ERK signalling pathway and promotes cell proliferation of hepatocellular carcinoma. Wang YP, Huang LY, Sun WM, Zhang ZZ, Fang JZ, Wei BF, Wu BH, Han ZG. Cancer Lett. 337 96-106 (2013)
  2. Structural Basis of the High Affinity Interaction between the Alphavirus Nonstructural Protein-3 (nsP3) and the SH3 Domain of Amphiphysin-2. Tossavainen H, Aitio O, Hellman M, Saksela K, Permi P. J. Biol. Chem. 291 16307-16317 (2016)
  3. The eukaryotic linear motif resource - 2018 update. Gouw M, Michael S, Sámano-Sánchez H, Kumar M, Zeke A, Lang B, Bely B, Chemes LB, Davey NE, Deng Z, Diella F, Gürth CM, Huber AK, Kleinsorg S, Schlegel LS, Palopoli N, Roey KV, Altenberg B, Reményi A, Dinkel H, Gibson TJ. Nucleic Acids Res. 46 D428-D434 (2018)
  4. BAI1-Associated Protein 2-Like 1 (BAIAP2L1) Is a Potential Biomarker in Ovarian Cancer. Chao A, Tsai CL, Jung SM, Chuang WC, Kao C, Hsu A, Chen SH, Lin CY, Lee YC, Lee YS, Wang TH, Wang HS, Lai CH. PLoS ONE 10 e0133081 (2015)
  5. Selective 1 Hα NMR Methods Reveal Functionally Relevant Proline cis/trans Isomers in Intrinsically Disordered Proteins: Characterization of Minor Forms, Effects of Phosphorylation, and Occurrence in Proteome. Sebák F, Ecsédi P, Bermel W, Luy B, Nyitray L, Bodor A. Angew Chem Int Ed Engl 61 e202108361 (2022)
  6. Host-pathogen crosstalking: the mastery of taking the helm of the host. Koutsotoli A, Tzakos AG. Structure 20 1613-1615 (2012)
  7. FBP21's C-Terminal Domain Remains Dynamic When Wrapped around the c-Sec63 Unit of Brr2 Helicase. Sticht J, Bertazzon M, Henning LM, Licha JR, Abualrous ET, Freund C. Biophys J 116 406-418 (2019)
  8. HACANCOi: a new Hα-detected experiment for backbone resonance assignment of intrinsically disordered proteins. Karjalainen M, Tossavainen H, Hellman M, Permi P. J Biomol NMR 74 741-752 (2020)
  9. IRTKS (BAIAP2L1) Elongates Epithelial Microvilli Using EPS8-Dependent and Independent Mechanisms. Postema MM, Grega-Larson NE, Neininger AC, Tyska MJ. Curr. Biol. 28 2876-2888.e4 (2018)
  10. Screening for host proteins interacting with Escherichia coli O157:H7 EspF using bimolecular fluorescence complementation. Hua Y, Ju J, Wang X, Zhang B, Zhao W, Zhang Q, Feng Y, Ma W, Wan C. Future Microbiol 13 37-58 (2018)
  11. 1H, 13C, and 15N NMR chemical shift assignment of the complex formed by the first EPEC EspF repeat and N-WASP GTPase binding domain. Karjalainen M, Hellman M, Tossavainen H, Permi P. Biomol NMR Assign 15 213-217 (2021)
  12. Decreased temperature increases the expression of a disordered bacterial late embryogenesis abundant (LEA) protein that enhances natural transformation. Maula T, Vahvelainen N, Tossavainen H, Koivunen T, T Pöllänen M, Johansson A, Permi P, Ihalin R. Virulence 12 1239-1257 (2021)
  13. Genomic Properties and Temporal Analysis of the Interaction of an Invasive Escherichia albertii With Epithelial Cells. Romão FT, Martins FH, Hernandes RT, Ooka T, Santos FF, Yamamoto D, Bonfim-Melo A, Jones N, Hayashi T, Elias WP, Sperandio V, Gomes TAT. Front Cell Infect Microbiol 10 571088 (2020)
  14. Redundant functions of I-BAR family members, IRSp53 and IRTKS, are essential for embryonic development. Chou AM, Sem KP, Lam WJ, Ahmed S, Lim CY. Sci Rep 7 40485 (2017)
  15. Structural and Functional Insights Into Lysostaphin-Substrate Interaction. Tossavainen H, Raulinaitis V, Kauppinen L, Pentikäinen U, Maaheimo H, Permi P. Front Mol Biosci 5 60 (2018)


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