Binding of Dr adhesins of Escherichia coli to carcinoembryonic antigen triggers receptor dissociation.
Carcinoembryonic antigen (CEA)-related cell adhesion molecules (CEACAMs) are host receptors for the Dr family of adhesins of Escherichia coli. To define the mechanism for binding of Dr adhesins to CEACAM receptors, we carried out structural studies on the N-terminal domain of CEA and its complex with the Dr adhesin. The crystal structure of CEA reveals a dimer similar to other dimers formed by receptors with IgV-like domains. The structure of the CEA/Dr adhesin complex is proposed based on NMR spectroscopy and mutagenesis data in combination with biochemical characterization. The Dr adhesin/CEA interface overlaps appreciably with the region responsible for CEA dimerization. Binding kinetics, mutational analysis and spectroscopic examination of CEA dimers suggest that Dr adhesins can dissociate CEA dimers prior to the binding of monomeric forms. Our conclusions include a plausible mechanism for how E. coli, and perhaps other bacterial and viral pathogens, exploit CEACAMs. The present structure of the complex provides a powerful tool for the design of novel inhibitory strategies to treat E. coli infections.
Korotkova
Natalia
N
Department of Microbiology, University of Washington, Seattle, WA 98195-7242, USA.
Yang
Yi
Y
Le Trong
Isolde
I
Cota
Ernesto
E
Demeler
Borries
B
Marchant
Jan
J
Thomas
Wendy E
WE
Stenkamp
Ronald E
RE
Moseley
Steve L
SL
Matthews
Steve
S
D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism; D018830:Adhesins, Escherichia coli / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002272:Carcinoembryonic Antigen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D018360:Crystallography, X-Ray; D019281:Dimerization; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D013050:Spectrometry, Fluorescence; D020349:Surface Plasmon Resonance / Q000379:methods; D014461:Ultracentrifugation
D018829:Adhesins, Bacterial; D018830:Adhesins, Escherichia coli; C108509:AfaE protein, E coli; D002272:Carcinoembryonic Antigen; C465564:Dr adhesin, E coli; C465563:DraE protein, E coli; D029968:Escherichia coli Proteins