title: The Moraxella adhesin UspA1 binds to its human CEACAM1 receptor by a deformable trimeric coiled-coil.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Bristol, Bristol, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Conners
authors.forename: Darryl J
authors.initials: DJ
authors.lastname: Hill
authors.forename: Elena
authors.initials: E
authors.lastname: Borodina
authors.forename: Christopher
authors.initials: C
authors.lastname: Agnew
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Daniell
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Burton
authors.forename: Richard B
authors.initials: RB
authors.lastname: Sessions
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Clarke
authors.forename: Lucy E
authors.initials: LE
authors.lastname: Catto
authors.forename: Donna
authors.initials: D
authors.lastname: Lammie
authors.forename: Timothy
authors.initials: T
authors.lastname: Wess
authors.forename: R Leo
authors.initials: RL
authors.lastname: Brady
authors.forename: Mumtaz
authors.initials: M
authors.lastname: Virji
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry / Q000378:metabolism*; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011956:Receptors, Cell Surface; D013816:Thermodynamics
chemical_list: D018829:Adhesins, Bacterial; D015703:Antigens, CD; D001425:Bacterial Outer Membrane Proteins; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D011956:Receptors, Cell Surface; C089675:UspA protein, Moraxella catarrhalis; C045157:adhesin, Moraxella