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Article Dans Une Revue Communications Biology Année : 2024

The pathogen-encoded signalling receptor Tir exploits host-like intrinsic disorder for infection

Marta Vieira
  • Fonction : Auteur
Guillem Hernandez
Qiyun Zhong
  • Fonction : Auteur
Miguel Arbesú
Tiago Veloso
  • Fonction : Auteur
Tiago Gomes
Maria Martins
Hugo Monteiro
  • Fonction : Auteur
Carlos Frazão
  • Fonction : Auteur
Gad Frankel
Tiago Cordeiro

Résumé

Abstract The translocated intimin receptor (Tir) is an essential type III secretion system (T3SS) effector of attaching and effacing pathogens contributing to the global foodborne disease burden. Tir acts as a cell-surface receptor in host cells, rewiring intracellular processes by targeting multiple host proteins. We investigated the molecular basis for Tir’s binding diversity in signalling, finding that Tir is a disordered protein with host-like binding motifs. Unexpectedly, also are several other T3SS effectors. By an integrative approach, we reveal that Tir dimerises via an antiparallel OB-fold within a highly disordered N-terminal cytosolic domain. Also, it has a long disordered C-terminal cytosolic domain partially structured at host-like motifs that bind lipids. Membrane affinity depends on lipid composition and phosphorylation, highlighting a previously unrecognised host interaction impacting Tir-induced actin polymerisation and cell death. Furthermore, multi-site tyrosine phosphorylation enables Tir to engage host SH2 domains in a multivalent fuzzy complex, consistent with Tir’s scaffolding role and binding promiscuity. Our findings provide insights into the intracellular Tir domains, highlighting the ability of T3SS effectors to exploit host-like protein disorder as a strategy for host evasion.

Dates et versions

hal-04516018 , version 1 (21-03-2024)

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Citer

Marta Vieira, Guillem Hernandez, Qiyun Zhong, Miguel Arbesú, Tiago Veloso, et al.. The pathogen-encoded signalling receptor Tir exploits host-like intrinsic disorder for infection. Communications Biology, 2024, 7 (1), pp.179. ⟨10.1038/s42003-024-05856-9⟩. ⟨hal-04516018⟩

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