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

Abhilash Padavannil; Chacko Jobichen; Erez Mills; Adrian Velazquez-Campoy; Mo Li; Ka Yin Leung; Yu Keung Mok; Ilan Rosenshine; J. Sivaraman

doi:10.1038/ncomms3546

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

Abhilash Padavannil, Chacko Jobichen, Erez Mills, Adrian Velazquez-Campoy, Mo Li, Ka Yin Leung, Yu Keung Mok, Ilan Rosenshine, J. Sivaraman^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

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.

Original language	English
Article number	2546
Journal	Nature Communications
Volume	4
DOIs	https://doi.org/10.1038/ncomms3546
State	Published - 2013
Externally published	Yes

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@article{a0aa7b06ee544db5947b30f587ad3088,

title = "Structure of GrlR-GrlA complex that prevents GrlA activation of virulence genes",

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.",

author = "Abhilash Padavannil and Chacko Jobichen and Erez Mills and Adrian Velazquez-Campoy and Mo Li and Leung, {Ka Yin} and Mok, {Yu Keung} and Ilan Rosenshine and J. Sivaraman",

year = "2013",

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journal = "Nature Communications",

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AU - Padavannil, Abhilash

AU - Jobichen, Chacko

AU - Mills, Erez

AU - Velazquez-Campoy, Adrian

AU - Li, Mo

AU - Leung, Ka Yin

AU - Mok, Yu Keung

AU - Rosenshine, Ilan

AU - Sivaraman, J.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

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