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dc.contributor.authorde Groot, Jens C
dc.contributor.authorSchlüter, Kai
dc.contributor.authorCarius, Yvonne
dc.contributor.authorQuedenau, Claudia
dc.contributor.authorVingadassalom, Didier
dc.contributor.authorFaix, Jan
dc.contributor.authorWeiss, Stefanie M
dc.contributor.authorReichelt, Joachim
dc.contributor.authorStandfuss-Gabisch, Christine
dc.contributor.authorLesser, Cammie F
dc.contributor.authorLeong, John M
dc.contributor.authorHeinz, Dirk W
dc.contributor.authorBüssow, Konrad
dc.contributor.authorStradal, Theresia E B
dc.date.accessioned2012-11-05T14:50:53Zen
dc.date.available2012-11-05T14:50:53Zen
dc.date.issued2011-09-07en
dc.identifier.citationStructural basis for complex formation between human IRSp53 and the translocated intimin receptor Tir of enterohemorrhagic E. coli. 2011, 19 (9):1294-306 Structureen_GB
dc.identifier.issn1878-4186en
dc.identifier.pmid21893288en
dc.identifier.doi10.1016/j.str.2011.06.015en
dc.identifier.urihttp://hdl.handle.net/10033/250993en
dc.description.abstractActin 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.
dc.language.isoenen
dc.rightsArchived with thanks to Structure (London, England : 1993)en_GB
dc.subject.meshAmino Acid Motifsen_GB
dc.subject.meshAmino Acid Substitutionen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshBinding Sitesen_GB
dc.subject.meshCOS Cellsen_GB
dc.subject.meshCalorimetryen_GB
dc.subject.meshCercopithecus aethiopsen_GB
dc.subject.meshCrystallography, X-Rayen_GB
dc.subject.meshEscherichia coli O157en_GB
dc.subject.meshEscherichia coli Proteinsen_GB
dc.subject.meshHost-Pathogen Interactionsen_GB
dc.subject.meshHumansen_GB
dc.subject.meshHydrogen Bondingen_GB
dc.subject.meshHydrophobic and Hydrophilic Interactionsen_GB
dc.subject.meshImmunoprecipitationen_GB
dc.subject.meshModels, Molecularen_GB
dc.subject.meshMutagenesis, Site-Directeden_GB
dc.subject.meshNerve Tissue Proteinsen_GB
dc.subject.meshPeptide Fragmentsen_GB
dc.subject.meshProtein Bindingen_GB
dc.subject.meshProtein Interaction Domains and Motifsen_GB
dc.subject.meshReceptors, Cell Surfaceen_GB
dc.subject.meshThermodynamicsen_GB
dc.titleStructural basis for complex formation between human IRSp53 and the translocated intimin receptor Tir of enterohemorrhagic E. coli.en
dc.typeArticleen
dc.contributor.departmentDivision of Structural Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.en_GB
dc.identifier.journalStructure (London, England : 1993)en_GB
refterms.dateFOA2018-06-13T05:37:29Z
html.description.abstractActin 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.


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