Structure of GrlR and the implication of its EDED motif in mediating the regulation of type III secretion system in EHEC.

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 o...

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Main Authors: Chacko Jobichen, Mo Li, Gal Yerushalmi, Yih Wan Tan, Yu-Keung Mok, Ilan Rosenshine, Ka Yin Leung, J Sivaraman
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2007-05-01
Series:PLoS Pathogens
Online Access:http://europepmc.org/articles/PMC1868957?pdf=render
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author Chacko Jobichen
Mo Li
Gal Yerushalmi
Yih Wan Tan
Yu-Keung Mok
Ilan Rosenshine
Ka Yin Leung
J Sivaraman
author_facet Chacko Jobichen
Mo Li
Gal Yerushalmi
Yih Wan Tan
Yu-Keung Mok
Ilan Rosenshine
Ka Yin Leung
J Sivaraman
author_sort Chacko Jobichen
collection DOAJ
description 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.
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spelling doaj.art-5c8452ac0b66480db6e1331587898a0f2022-12-21T19:09:07ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742007-05-0135e6910.1371/journal.ppat.0030069Structure of GrlR and the implication of its EDED motif in mediating the regulation of type III secretion system in EHEC.Chacko JobichenMo LiGal YerushalmiYih Wan TanYu-Keung MokIlan RosenshineKa Yin LeungJ SivaramanEnterohemorrhagic 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.http://europepmc.org/articles/PMC1868957?pdf=render
spellingShingle Chacko Jobichen
Mo Li
Gal Yerushalmi
Yih Wan Tan
Yu-Keung Mok
Ilan Rosenshine
Ka Yin Leung
J Sivaraman
Structure of GrlR and the implication of its EDED motif in mediating the regulation of type III secretion system in EHEC.
PLoS Pathogens
title Structure of GrlR and the implication of its EDED motif in mediating the regulation of type III secretion system in EHEC.
title_full Structure of GrlR and the implication of its EDED motif in mediating the regulation of type III secretion system in EHEC.
title_fullStr Structure of GrlR and the implication of its EDED motif in mediating the regulation of type III secretion system in EHEC.
title_full_unstemmed Structure of GrlR and the implication of its EDED motif in mediating the regulation of type III secretion system in EHEC.
title_short Structure of GrlR and the implication of its EDED motif in mediating the regulation of type III secretion system in EHEC.
title_sort structure of grlr and the implication of its eded motif in mediating the regulation of type iii secretion system in ehec
url http://europepmc.org/articles/PMC1868957?pdf=render
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