Structural basis of the interaction of the pyelonephritic E. coli adhesin to its human kidney receptor

PapG is the adhesin at the tip of the P pilus that mediates attachment of u ropathogenic 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 beta1-3Gal alpha1-4Gal beta1-4Glc linked to cer amide. Here, we present the crystal structures of a binary complex of the P apG receptor binding domain bound to GbO4 as well as the unbound form of th e adhesin. The biological importance of each of the residues involved in bi nding was investigated by site-directed mutagenesis. These studies provide a molecular snapshot of a host-pathogen interaction that determines the tro pism of uropathogenic E. coli for the human kidney and is critical to the p athogenesis of pyelonephritis.