title: Structural and functional studies of Escherichia coli aggregative adherence fimbriae (AAF/V) reveal a deficiency in extracellular matrix binding.
abstract: Enteroaggregative Escherichia coli (EAEC) is an emerging cause of acute and persistent diarrhea worldwide. The pathogenesis of different EAEC stains is complicated, however, the early essential step begins with attachment of EAEC to intestinal mucosa via aggregative adherence fimbriae (AAFs). Currently, five different variants have been identified, which all share a degree of similarity in the gene organization of their operons and sequences. Here, we report the solution structure of Agg5A from the AAF/V variant. While preserving the major structural features shared by all AAF members, only Agg5A possesses an inserted helix at the beginning of the donor strand, which together with altered surface electrostatics, renders the protein unable to interact with fibronectin. Hence, here we characterize the first AAF variant with a binding mode that varies from previously described AAFs.
authors.affiliation: Institute for Science and Environment, Roskilde University, Roskilde, Denmark; Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Rie
authors.initials: R
authors.lastname: Jønsson
authors.affiliation: Centre for Structural Biology, Department of Life Sciences, Imperial College London, South Kensington, London, United Kingdom.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Carsten
authors.initials: C
authors.lastname: Struve
authors.affiliation: Centre for Structural Biology, Department of Life Sciences, Imperial College London, South Kensington, London, United Kingdom.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: René
authors.initials: R
authors.lastname: Jørgensen
authors.affiliation: Centre for Structural Biology, Department of Life Sciences, Imperial College London, South Kensington, London, United Kingdom.
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Institute for Science and Environment, Roskilde University, Roskilde, Denmark.
authors.forename: Håvard
authors.initials: H
authors.lastname: Jenssen
authors.affiliation: Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark. Electronic address: kak@ssi.dk.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Krogfelt
authors.affiliation: Centre for Structural Biology, Department of Life Sciences, Imperial College London, South Kensington, London, United Kingdom. Electronic address: s.j.matthews@imperial.ac.uk.
authors.forename: Steve
authors.initials: S
authors.lastname: Matthews
mesh_terms: D018830:Adhesins, Escherichia coli / Q000378:metabolism; D000595:Amino Acid Sequence; D001422:Bacterial Adhesion / Q000502:physiology*; D004926:Escherichia coli / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000378:metabolism / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D010861:Fimbriae, Bacterial / Q000378:metabolism*; D006801:Humans; D016415:Sequence Alignment
chemical_list: D018830:Adhesins, Escherichia coli; D029968:Escherichia coli Proteins; D005353:Fibronectins
keywords: Agg5A; Aggregative adherence fimbriae; Chaperone-usher; Donor strand complementation; E. coli; Fibronectin; Pilin