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

TY - JOUR

T1 - Structure of GrlR and the implication of its EDED motif in mediating the regulation of type III secretion system in EHEC

AU - Jobichen, Chacko

AU - Li, Mo

AU - Yerushalmi, Gal

AU - Yih, Wan Tan

AU - Mok, Yu Keung

AU - Rosenshine, Ilan

AU - Ka, Yin Leung

AU - Sivaraman, J.

PY - 2007

Y1 - 2007

N2 - 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 Å resolution. It consists of a typical β-barrel fold with eight β-strands containing an internal hydrophobic cavity and a plug-like loop on one side of the barrel. Strong hydrophobic interactions between the two β-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.

AB - 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 Å resolution. It consists of a typical β-barrel fold with eight β-strands containing an internal hydrophobic cavity and a plug-like loop on one side of the barrel. Strong hydrophobic interactions between the two β-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.

UR - http://www.scopus.com/inward/record.url?scp=34249710237&partnerID=8YFLogxK

U2 - 10.1371/journal.ppat.0030069

DO - 10.1371/journal.ppat.0030069

M3 - 文章

C2 - 17511515

AN - SCOPUS:34249710237

SN - 1553-7366

VL - 3

SP - 639

EP - 646

JO - PLoS Pathogens

JF - PLoS Pathogens

IS - 5

ER -