title: Crystal structure of EHEC intimin: insights into the complementarity between EPEC and EHEC.
abstract: Enterohaemorrhagic E. coli (EHEC) O157:H7 is a primary food-borne bacterial pathogen capable of causing life-threatening human infections which poses a serious challenge to public health worldwide. Intimin, the bacterial outer-membrane protein, plays a key role in the initiating process of EHEC infection. This activity is dependent upon translocation of the intimin receptor (Tir), the intimin binding partner of the bacteria-encoded host cell surface protein. Intimin has attracted considerable attention due to its potential function as an antibacterial drug target. Here, we report the crystal structure of the Tir-binding domain of intimin (Int188) from E. coli O157:H7 at 2.8 Å resolution, together with a mutant (IntN916Y) at 2.6 Å. We also built the structural model of EHEC intimin-Tir complex and analyzed the key binding residues. It suggested that the binding pattern of intimin and Tir between EHEC and Enteropathogenic E. coli (EPEC) adopt a similar mode and they can complement with each other. Detailed structural comparison indicates that there are four major points of structural variations between EHEC and EPEC intimins: one in Domain I (Ig-like domain), the other three located in Domain II (C-type lectin-like domain). These variations result in different binding affinities. These findings provide structural insight into the binding pattern of intimin to Tir and the molecular mechanism of EHEC O157: H7.
authors.affiliation: Department of Clinical Microbiology and Clinical Immunology, College of Medical Laboratory, Third Military Medical University, Chongqing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yi
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Xuhu
authors.initials: X
authors.lastname: Mao
authors.forename: Hao
authors.initials: H
authors.lastname: Peng
authors.forename: Youjun
authors.initials: Y
authors.lastname: Feng
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fan
authors.forename: Guihua
authors.initials: G
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Guo
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yan
authors.forename: Hao
authors.initials: H
authors.lastname: Zeng
authors.forename: Quanming
authors.initials: Q
authors.lastname: Zou
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry*; D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray / Q000379:methods; D054324:Enterohemorrhagic Escherichia coli / Q000378:metabolism*; D054308:Enteropathogenic Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid
chemical_list: D018829:Adhesins, Bacterial; D029968:Escherichia coli Proteins; D011994:Recombinant Proteins; C073819:eaeA protein, E coli