Binding of Dr adhesins of Escherichia coli to carcinoembryonic antigen triggers receptor dissociation
Author/Creator ORCID
Date
Type of Work
Department
Program
Citation of Original Publication
Korotkova, Natalia, Yi Yang, Isolde Le Trong, et al. “Binding of Dr Adhesins of Escherichia Coli to Carcinoembryonic Antigen Triggers Receptor Dissociation.” Molecular Microbiology 67, no. 2 (2008): 420–34. https://doi.org/10.1111/j.1365-2958.2007.06054.x.
Rights
This is the peer reviewed version of the following article: Korotkova, Natalia, Yi Yang, Isolde Le Trong, et al. “Binding of Dr Adhesins of Escherichia Coli to Carcinoembryonic Antigen Triggers Receptor Dissociation.” Molecular Microbiology 67, no. 2 (2008): 420–34. https://doi.org/10.1111/j.1365-2958.2007.06054.x., which has been published in final form at https://doi.org/10.1111/j.1365-2958.2007.06054.x. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited
Subjects
Abstract
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.