title: Structural basis of the interaction of the pyelonephritic E. coli adhesin to its human kidney receptor.
abstract: PapG is the adhesin at the tip of the P pilus that mediates attachment of uropathogenic Escherichia coli to the uroepithelium of the human kidney. The human specific allele of PapG binds to globoside (GbO4), which consists of the tetrasaccharide GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc linked to ceramide. Here, we present the crystal structures of a binary complex of the PapG receptor binding domain bound to GbO4 as well as the unbound form of the adhesin. The biological importance of each of the residues involved in binding was investigated by site-directed mutagenesis. These studies provide a molecular snapshot of a host-pathogen interaction that determines the tropism of uropathogenic E. coli for the human kidney and is critical to the pathogenesis of pyelonephritis.
authors: Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
authors: K W
authors: KW
authors: Dodson
authors: J S
authors: JS
authors: Pinkner
authors: T
authors: T
authors: Rose
authors: G
authors: G
authors: Magnusson
authors: S J
authors: SJ
authors: Hultgren
authors: G
authors: G
authors: Waksman
mesh_terms: D018830:Adhesins, Escherichia coli / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000378:metabolism / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000378:metabolism; D005260:Female; D036781:Fimbriae Proteins; D010861:Fimbriae, Bacterial / Q000737:chemistry / Q000378:metabolism; D005915:Globosides / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011704:Pyelonephritis / Q000382:microbiology; D016415:Sequence Alignment; D019459:Urothelium / Q000378:metabolism*
chemical_list: D018830:Adhesins, Escherichia coli; D005915:Globosides; C092426:PapG protein, E coli; D036781:Fimbriae Proteins