structure of grlr and the implication of its eded motif in mediating the regulation of type iii secretion system in ehecgrlr结构,它在调节调节ed图案的含义在肠出血性大肠杆菌iii型分泌系统.pdf

Structure of GrlR and the Implication of Its EDED Motif in Mediating the Regulation of Type III Secretion System in EHEC 1[ 1[ 2 1 1 2 1 Chacko Jobichen , Mo Li , Gal Yerushalmi , Yih Wan Tan , Yu-Keung Mok , Ilan Rosenshine , Ka Yin Leung , 1* J. Sivaraman 1 Department of Biological Sciences, National University of Singapore, Singapore, 2 Department of Molecular Genetics and Biotechnology, Faculty of Medicine, The Hebrew University, Jerusalem, Israel 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 b-barrel fold with eight b-strands containing an internal hydrophobic cavity and a plug-like loop on one side of the barrel. Strong hydrophobic interactions between the two b- 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