1KLF

FIMH ADHESIN-FIMC CHAPERONE COMPLEX WITH D-MANNOSE

Summary for 1KLF

• Entry DOI: 10.2210/pdb1klf/pdb
• Related: 1KIU 1QUN
• Descriptor: CHAPERONE PROTEIN FIMC, FIMH PROTEIN, alpha-D-mannopyranose, ... (4 entities in total)
• Functional Keywords: adhesin-chaperone complex, mannose-bound, chaperone-adhesin complex complex, chaperone/adhesin complex
• Biological source: Escherichia coli; More
• Total number of polymer chains: 16
• Total formula weight: 415884.15

Authors

Hung, C.S.,Bouckaert, J. (deposition date: 2001-12-11, release date: 2002-06-05, Last modification date: 2024-10-30)

Primary citation

Hung, C.S.,Bouckaert, J.,Hung, D.,Pinkner, J.,Widberg, C.,DeFusco, A.,Auguste, C.G.,Strouse, R.,Langermann, S.,Waksman, G.,Hultgren, S.J.
Structural basis of tropism of Escherichia coli to the bladder during urinary tract infection.
Mol.Microbiol., 44:903-915, 2002

PubMed Abstract: The first step in the colonization of the human urinary tract by pathogenic Escherichia coli is the mannose-sensitive binding of FimH, the adhesin present at the tip of type 1 pili, to the bladder epithelium. We elucidated crystallographically the interactions of FimH with D-mannose. The unique site binding pocket occupied by D-mannose was probed using site-directed mutagenesis. All but one of the mutants examined had greatly diminished mannose-binding activity and had also lost the ability to bind human bladder cells. The binding activity of the mono-saccharide D-mannose was delineated from this of mannotriose (Man(alpha 1-3)[Man(alpha 1-6)]Man) by generating mutants that abolished D-mannose binding but retained mannotriose binding activity. Our structure/function analysis demonstrated that the binding of the monosaccharide alpha-D-mannose is the primary bladder cell receptor for uropathogenic E. coli and that this event requires a highly conserved FimH binding pocket. The residues in the FimH mannose-binding pocket were sequenced and found to be invariant in over 200 uropathogenic strains of E. coli. Only enterohaemorrhagic E. coli (EHEC) possess a sequence variation within the mannose-binding pocket of FimH, suggesting a naturally occurring mechanism of attenuation in EHEC bacteria that would prevent them from being targeted to the urinary tract.

PubMed: 12010488
DOI: 10.1046/j.1365-2958.2002.02915.x

Experimental method

X-RAY DIFFRACTION (2.79 Å)