The Moraxella adhesin UspA1 binds to its human CEACAM1 receptor by a deformable trimeric coiled-coil

Autor: R. Leo Brady, Richard B. Sessions, Anthony R. Clarke, Darryl J. Hill, Christopher R. Agnew, Rebecca Conners, Elena Borodina, Tim J Wess, Mumtaz Virji, Lucy E. Catto, Donna Lammie, Sarah J. Daniell, Nicholas M. Burton
Rok vydání: 2008
Předmět:
Models
Molecular
Receptors
Cell Surface
Plasma protein binding
Crystallography
X-Ray
Protein Structure
Secondary
Article
General Biochemistry
Genetics and Molecular Biology
Microbiology
Moraxella catarrhalis
03 medical and health sciences
Antigens
CD
bacterial adhesin
coiled-coil
Humans
adhesion molecules
Adhesins
Bacterial
Molecular Biology
Moraxella
X-ray crystallography
030304 developmental biology
Coiled coil
0303 health sciences
Binding Sites
General Immunology and Microbiology
biology
030306 microbiology
Circular Dichroism
General Neuroscience
SAXS
biology.organism_classification
Ligand (biochemistry)
3. Good health
Bacterial adhesin
A-site
Mutagenesis
Site-Directed
Autotransporter domain
Biophysics
Thermodynamics
Cell Adhesion Molecules
Bacterial Outer Membrane Proteins
Protein Binding
Zdroj: The EMBO Journal
ISSN: 1460-2075
0261-4189
DOI: 10.1038/emboj.2008.101
Popis: Moraxella catarrhalis is a ubiquitous human-specific bacterium commonly associated with upper and lower respiratory tract infections, including otitis media, sinusitis and chronic obstructive pulmonary disease. The bacterium uses an autotransporter protein UspA1 to target an important human cellular receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Using X-ray crystallography, we show that the CEACAM1 receptor-binding region of UspA1 unusually consists of an extended, rod-like left-handed trimeric coiled-coil. Mutagenesis and binding studies of UspA1 and the N-domain of CEACAM1 have been used to delineate the interacting surfaces between ligand and receptor and guide assembly of the complex. However, solution scattering, molecular modelling and electron microscopy analyses all indicate that significant bending of the UspA1 coiled-coil stalk also occurs. This explains how UspA1 can engage CEACAM1 at a site far distant from its head group, permitting closer proximity of the respective cell surfaces during infection.
Databáze: OpenAIRE
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