PDBsum entry: 2qst

Cell adhesion

PDB id: 2qst

Contents

Protein chains

111 a.a. *

Waters ×11

* Residue conservation analysis

PDB id:

2qst

Name:

Cell adhesion

Title:

Crystal structure of the v39c mutant of the n-terminal domain of carcinoembryonic antigen (cea)

Structure:

Carcinoembryonic antigen-related cell adhesion molecule 5. Chain: a, b. Fragment: n-terminal domain of cea (unp residues 34-110). Synonym: carcinoembryonic antigen, cea, meconium antigen 100, cd66e antigen. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ceacam5, cea. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.90Å R-factor: 0.215 R-free: 0.250

Authors:

I.Le Trong,N.Korotkova,S.L.Moseley,R.E.Stenkamp

Key ref:

N.Korotkova et al. (2008). Binding of Dr adhesins of Escherichia coli to carcinoembryonic antigen triggers receptor dissociation. Mol Microbiol, 67, 420-434. PubMed id: 18086185 DOI: 10.1111/j.1365-2958.2007.06054.x

Date:

31-Jul-07 Release date: 01-Jan-08

Protein chains

P06731  (CEAM5_HUMAN) -  Carcinoembryonic antigen-related cell adhesion molecule 5

Seq: 702 a.a.

Struc: 111 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1111/j.1365-2958.2007.06054.x

Mol Microbiol 67:420-434 (2008)

PubMed id: 18086185

Binding of Dr adhesins of Escherichia coli to carcinoembryonic antigen triggers receptor dissociation.

N.Korotkova, Y.Yang, I.Le Trong, E.Cota, B.Demeler, J.Marchant, W.E.Thomas, R.E.Stenkamp, S.L.Moseley, S.Matthews.

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.