PDBsum entry 1j8s

Structural protein

PDB id: 1j8s

Contents

Protein chain

196 a.a. *

Waters ×111

* Residue conservation analysis

PDB id:

1j8s

Name:

Structural protein

Title:

Papg adhesin receptor binding domain-unbound form

Structure:

Pyelonephritic adhesin. Chain: a. Fragment: papg receptor-binding domain. Synonym: papg adhesin

Source:

Escherichia coli. Organism_taxid: 562

Resolution:

2.10Å R-factor: 0.232 R-free: 0.255

Authors:

K.W.Dodson,J.S.Pinkner,T.Rose,G.Magnusson,S.J.Hultgren,G.Waksman

Key ref:

K.W.Dodson et al. (2001). Structural basis of the interaction of the pyelonephritic E. coli adhesin to its human kidney receptor. Cell, 105, 733-743. PubMed id: 11440716 DOI: 10.1016/S0092-8674(01)00388-9

Date:

22-May-01 Release date: 22-Jun-01

Protein chain

Q47450  (PAPG2_ECOLX) -  Fimbrial adhesin PapGII from Escherichia coli

Seq: 336 a.a.

Struc: 196 a.a.

DOI no: 10.1016/S0092-8674(01)00388-9

Cell 105:733-743 (2001)

PubMed id: 11440716

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

K.W.Dodson, J.S.Pinkner, T.Rose, G.Magnusson, S.J.Hultgren, G.Waksman.

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.

Selected figure(s)

Figure 2.
Figure 2. The GbO4 Binding Site(A) Stereo-diagram of binding site. The protein backbone is in ribbon representation as in Figure 1B and secondary structures are labeled according to Figure 1B. Residues in the protein interacting with the GbO4 receptor are in ball-and-stick representation with carbon atoms in gray, oxygen atoms in red, and nitrogen atoms in blue. Receptor residues are in ball-and-stick representation with carbon atoms in silver, and oxygen and nitrogen atoms as in the protein. Water molecules involved in interactions between the protein and receptor residues are in ball representation color-coded in magenta and labeled W1 to 7. Receptor residues are labeled A to D as in Figure 1B.(B) Schematic representation of interactions between protein and receptor. Direct polar interactions are indicated by red arrows. Water-mediated interactions are indicated by blue arrows. Brackets and arrows in green indicate contacts with aromatic/hydrophobic platforms

Figure 5.
Figure 5. Model of the Interactions of the PapGII Adhesin at the Membrane(A) A P pilus. The PapG adhesin is located at the thin tip of the pilus. Note the bend at the tip of the pilus, which places the PapG adhesin in a proper orientation for side-on binding to the membrane.(B) Model of PapGII receptor binding domain interacting with GbO4-ceramide. This model was generated by attaching a ceramide group to the Galβ1-4Glc moiety of GbO4 such that the resulting Galβ1-4Glcβ-ceramide would adopt a configuration similar to that crystallographically observed for a digalactoside-ceramide (Pascher et al., 1992). The molecular surface is that of the protein, color-coded according to charge, blue for positive (Arg and Lys) and red for negative (Glu and Asp). Charged residues which could potentially interact with the head groups of the eukaryotic membrane are labeled. The GbO4-ceramide is in CPK representation with carbon atoms in green, oxygen atoms in red, and nitrogen atoms in blue.(C) Model of uroepithelium. The GbO4-ceramide is represented as in (B) and is labeled “GbO4”

The above figures are reprinted by permission from Cell Press: Cell (2001, 105, 733-743) copyright 2001.

Figures were selected by an automated process.