» Articles » PMID: 17511515

Structure of GrlR and the Implication of Its EDED Motif in Mediating the Regulation of Type III Secretion System in EHEC

Overview
Journal PLoS Pathog
Specialty Microbiology
Date 2007 May 22
PMID 17511515
Citations 20
Authors
Affiliations
Soon will be listed here.
Abstract

Enterohemorrhagic Escherichia coli (EHEC) is a common cause of severe hemorrhagic colitis. EHEC's virulence is dependent upon a type III secretion system (TTSS) encoded by 41 genes. These genes are organized in several operons clustered in the locus of enterocyte effacement. Most of the locus of enterocyte effacement genes, including grlA and grlR, are positively regulated by Ler, and Ler expression is positively and negatively modulated by GrlA and GrlR, respectively. However, the molecular basis for the GrlA and GrlR activity is still elusive. We have determined the crystal structure of GrlR at 1.9 A resolution. It consists of a typical beta-barrel fold with eight beta-strands containing an internal hydrophobic cavity and a plug-like loop on one side of the barrel. Strong hydrophobic interactions between the two beta-barrels maintain the dimeric architecture of GrlR. Furthermore, a unique surface-exposed EDED (Glu-Asp-Glu-Asp) motif is identified to be critical for GrlA-GrlR interaction and for the repressive activity of GrlR. This study contributes a novel molecular insight into the mechanism of GrlR function.

Citing Articles

Phenotypic diversity of type III secretion system activity in enteropathogenic clinical isolates.

Contreras C, Hazen T, Guadarrama C, Cervantes-Rivera R, Ochoa T, Vinuesa P J Med Microbiol. 2024; 73(10).

PMID: 39432330 PMC: 11493143. DOI: 10.1099/jmm.0.001907.


GrlR, a negative regulator in enteropathogenic , also represses the expression of LEE virulence genes independently of its interaction with its cognate partner GrlA.

Lara-Ochoa C, Huerta-Saquero A, Medrano-Lopez A, Deng W, Finlay B, Martinez-Laguna Y Front Microbiol. 2023; 14:1063368.

PMID: 36876072 PMC: 9979310. DOI: 10.3389/fmicb.2023.1063368.


The two sRNAs OmrA and OmrB indirectly repress transcription from the LEE1 promoter of enteropathogenic Escherichia coli.

Muche S, El-Fenej J, Mihaita A, Mrozek Z, Cleary S, Critelli B Folia Microbiol (Praha). 2022; 68(3):415-430.

PMID: 36547806 DOI: 10.1007/s12223-022-01025-9.


The transcription factor GrlA is regulated by subcellular compartmentalization and activated in response to mechanical stimuli.

Sirisaengtaksin N, Odem M, Bosserman R, Flores E, Krachler A Proc Natl Acad Sci U S A. 2020; 117(17):9519-9528.

PMID: 32277032 PMC: 7196828. DOI: 10.1073/pnas.1917500117.


The Small Regulatory RNA Spot42 Inhibits Indole Biosynthesis to Negatively Regulate the Locus of Enterocyte Effacement of Enteropathogenic Escherichia coli.

Bhatt S, Jenkins V, Mason E, Muche S Microorganisms. 2017; 5(4).

PMID: 29194362 PMC: 5748587. DOI: 10.3390/microorganisms5040078.


References
1.
Polotsky Y, Dragunskaya E, Seliverstova V, AVDEEVA T, Chakhutinskaya M, KETYI I . Pathogenic effect of enterotoxigenic Escherichia coli and Escherichia coli causing infantile diarrhoea. Acta Microbiol Acad Sci Hung. 1977; 24(3):221-36. View

2.
Hayward R, Leong J, Koronakis V, Campellone K . Exploiting pathogenic Escherichia coli to model transmembrane receptor signalling. Nat Rev Microbiol. 2006; 4(5):358-70. DOI: 10.1038/nrmicro1391. View

3.
Hautefort I, Proenca M, Hinton J . Single-copy green fluorescent protein gene fusions allow accurate measurement of Salmonella gene expression in vitro and during infection of mammalian cells. Appl Environ Microbiol. 2003; 69(12):7480-91. PMC: 310007. DOI: 10.1128/AEM.69.12.7480-7491.2003. View

4.
Creasey E, Delahay R, Daniell S, Frankel G . Yeast two-hybrid system survey of interactions between LEE-encoded proteins of enteropathogenic Escherichia coli. Microbiology (Reading). 2003; 149(Pt 8):2093-2106. DOI: 10.1099/mic.0.26355-0. View

5.
Berman H, Westbrook J, Feng Z, Gilliland G, Bhat T, Weissig H . The Protein Data Bank. Nucleic Acids Res. 1999; 28(1):235-42. PMC: 102472. DOI: 10.1093/nar/28.1.235. View