title: Structural basis for complex formation between human IRSp53 and the translocated intimin receptor Tir of enterohemorrhagic E. coli.
abstract: Actin assembly beneath enterohemorrhagic E. coli (EHEC) attached to its host cell is triggered by the intracellular interaction of its translocated effector proteins Tir and EspF(U) with human IRSp53 family proteins and N-WASP. Here, we report the structure of the N-terminal I-BAR domain of IRSp53 in complex with a Tir-derived peptide, in which the homodimeric I-BAR domain binds two Tir molecules aligned in parallel. This arrangement provides a protein scaffold linking the bacterium to the host cell's actin polymerization machinery. The structure uncovers a specific peptide-binding site on the I-BAR surface, conserved between IRSp53 and IRTKS. The Tir Asn-Pro-Tyr (NPY) motif, essential for pedestal formation, is specifically recognized by this binding site. The site was confirmed by mutagenesis and in vivo-binding assays. It is possible that IRSp53 utilizes the NPY-binding site for additional interactions with as yet unknown partners within the host cell.
authors: Division of Structural Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
authors: Jens C
authors: JC
authors: de Groot
authors: Kai
authors: K
authors: Schlüter
authors: Yvonne
authors: Y
authors: Carius
authors: Claudia
authors: C
authors: Quedenau
authors: Didier
authors: D
authors: Vingadassalom
authors: Jan
authors: J
authors: Faix
authors: Stefanie M
authors: SM
authors: Weiss
authors: Joachim
authors: J
authors: Reichelt
authors: Christine
authors: C
authors: Standfuss-Gabisch
authors: Cammie F
authors: CF
authors: Lesser
authors: John M
authors: JM
authors: Leong
authors: Dirk W
authors: DW
authors: Heinz
authors: Konrad
authors: K
authors: Büssow
authors: Theresia E B
authors: TE
authors: Stradal
mesh_terms: D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002151:Calorimetry; D002522:Chlorocebus aethiops; D018360:Crystallography, X-Ray; D019453:Escherichia coli O157; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics; D054884:Host-Pathogen Interactions; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D047468:Immunoprecipitation; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics; D013816:Thermodynamics
chemical_list: C119539:BAIAP2 protein, human; D029968:Escherichia coli Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C109287:Tir protein, E coli