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  • The EMBO Journal (2008) 27, 1779 - 1789
  • doi:10.1038/emboj.2008.101

Published online: 22 May 2008

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

Rebecca Conners1,a, Darryl J Hill2,a, Elena Borodina2, Christopher Agnew1, Sarah J Daniell2, Nicholas M Burton1, Richard B Sessions1, Anthony R Clarke1, Lucy E Catto1, Donna Lammie3, Timothy Wess3, R Leo Brady1 and Mumtaz Virji2

  1. Department of Biochemistry, University of Bristol, Bristol, UK
  2. Department of Cellular and Molecular Medicine, University of Bristol, Bristol, UK
  3. Cardiff School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK

Correspondence to:

R Leo Brady, Department of Biochemistry, University of Bristol, University Walk, Bristol BS8 1TD, UK. Tel.: +44 117 331 2150; Fax:+44 117 331 2168; E-mail: L.Brady@bristol.ac.uk

Mumtaz Virji, Department of Cellular and Molecular Medicine, University of Bristol, University Walk, Bristol BS8 1TD, UK. Tel. & Fax: +44 117 331 2035; E-mail: M.Virji@bristol.ac.uk

aThese authors contributed equally to this work

Received 16 August 2007; Accepted 23 April 2008

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.

  • Keywords:

    • adhesion molecules,
    • bacterial adhesin,
    • coiled-coil,
    • SAXS,
    • X-ray crystallography

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The EMBO Journal is published by Nature Publishing Group on behalf of European Molecular Biology Organization