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Structure of GrlR-GrlA complex that prevents GrlA activation of virulence genes.

Padavannil A, Jobichen C, Mills E, Velazquez-Campoy A, Li M, Leung KY, Mok YK, Rosenshine I, Sivaraman J
Nat Commun 4 2546 (2013)
Cited: 28 times
EuropePMC logo PMID: 24092262

Abstract

The locus of enterocyte effacement (LEE) is essential for virulence of enterohaemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC). The 41 genes of the LEE encode type III secretion system proteins and three associated regulators: Ler, GrlA and GrlR. Ler is a positive regulator for most of the LEE operons, including grlRA. GrlA controls the expression of ler, ehxCABD and flhDC operons. GrlR binds to GrlA and suppresses its function. Here we report the crystal structure of GrlR-GrlAΔ (aa 1-106) complex (2:1) and its functional characterization. We show that GrlR interacts with the Helix-Turn-Helix motif of GrlA. Moreover, GrlA binds to the promoter DNA fragments of ler, ehxCABD and flhDC, and GrlR outcompetes with these promoter DNA sequences for the Helix-Turn-Helix motif of GrlA. These findings provide mechanistic insight into a regulatory module for the virulence of EPEC and EHEC, two important pathogens that cause devastating diseases.

Articles - 4kt5 mentioned but not cited (1)

  1. Bile salt receptor complex activates a pathogenic type III secretion system. Li P, Rivera-Cancel G, Kinch LN, Salomon D, Tomchick DR, Grishin NV, Orth K. Elife 5 e15718 (2016)


Reviews citing this publication (7)

  1. Type Three Secretion System in Attaching and Effacing Pathogens. Gaytán MO, Martínez-Santos VI, Soto E, González-Pedrajo B. Front Cell Infect Microbiol 6 129 (2016)
  2. Regulation of the Locus of Enterocyte Effacement in Attaching and Effacing Pathogens. Furniss RCD, Clements A. J Bacteriol 200 e00336-17 (2018)
  3. From ingestion to colonization: the influence of the host environment on regulation of the LEE encoded type III secretion system in enterohaemorrhagic Escherichia coli. Connolly JP, Finlay BB, Roe AJ. Front Microbiol 6 568 (2015)
  4. Environment Controls LEE Regulation in Enteropathogenic Escherichia coli. Platenkamp A, Mellies JL. Front Microbiol 9 1694 (2018)
  5. Control freaks-signals and cues governing the regulation of virulence in attaching and effacing pathogens. Turner NCA, Connolly JPR, Roe AJ. Biochem Soc Trans 47 229-238 (2019)
  6. Staying out or Going in? The Interplay between Type 3 and Type 5 Secretion Systems in Adhesion and Invasion of Enterobacterial Pathogens. Whelan R, McVicker G, Leo JC. Int J Mol Sci 21 E4102 (2020)
  7. Genomic island-encoded regulatory proteins in enterohemorrhagic Escherichia coli O157:H7. Wang F, Sun H, Kang C, Yan J, Chen J, Feng X, Yang B. Virulence 15 2313407 (2024)

Articles citing this publication (20)



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