title: The structural basis of receptor-binding by Escherichia coli associated with diarrhea and septicemia.
abstract: GafD in Escherichia coli G (F17) fimbriae is associated with diarrheal disease, and the structure of the ligand-binding domain, GafD1-178, has been determined at 1.7A resolution in the presence of the receptor sugar N-acetyl-D-glucosamine. The overall fold is a beta-barrel jelly-roll fold. The ligand-binding site was identified and localized to the side of the molecule. Receptor binding is mediated by side-chain as well main-chain interactions. Ala43-Asn44, Ser116-Thr117 form the sugar acetamide specificity pocket, while Asp88 confers tight binding and Trp109 appears to position the ligand. There is a disulfide bond that rigidifies the acetamide specificity pocket. The three fimbrial lectins, GafD, FimH and PapG share similar beta-barrel folds but display different ligand-binding regions and disulfide-bond patterns. We suggest an evolutionary path for the evolution of the very diverse fimbrial lectins from a common ancestral fold.
authors.affiliation: Structural Biology and Biophysics, Institute of Biotechnology, Viikki Biocenter, University of Helsinki, PO Box 56, FIN-00014 Helsinki, Finland.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Merckel
authors.forename: Jarna
authors.initials: J
authors.lastname: Tanskanen
authors.forename: Sanna
authors.initials: S
authors.lastname: Edelman
authors.forename: Benita
authors.initials: B
authors.lastname: Westerlund-Wikström
authors.forename: Timo K
authors.initials: TK
authors.lastname: Korhonen
authors.forename: Adrian
authors.initials: A
authors.lastname: Goldman
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism; D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D001422:Bacterial Adhesion; D001665:Binding Sites; D018360:Crystallography, X-Ray; D003967:Diarrhea / Q000382:microbiology*; D004220:Disulfides; D004926:Escherichia coli / Q000737:chemistry* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism*; D036781:Fimbriae Proteins / Q000737:chemistry* / Q000378:metabolism*; D006860:Hydrogen Bonding; D037102:Lectins / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D018805:Sepsis / Q000382:microbiology*; D013329:Structure-Activity Relationship
chemical_list: D018829:Adhesins, Bacterial; D004220:Disulfides; D029968:Escherichia coli Proteins; C092493:GafD protein, E coli; D037102:Lectins; D008024:Ligands; D036781:Fimbriae Proteins; D000117:Acetylglucosamine