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

EMBO J. 2008 Jun 18;27(12):1779-89. doi: 10.1038/emboj.2008.101. Epub 2008 May 22.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / chemistry
  • Adhesins, Bacterial / metabolism*
  • Antigens, CD / chemistry
  • Antigens, CD / metabolism*
  • Bacterial Outer Membrane Proteins / chemistry
  • Bacterial Outer Membrane Proteins / metabolism*
  • Binding Sites
  • Cell Adhesion Molecules / chemistry
  • Cell Adhesion Molecules / metabolism*
  • Circular Dichroism
  • Crystallography, X-Ray
  • Humans
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Protein Binding
  • Protein Structure, Secondary
  • Receptors, Cell Surface
  • Thermodynamics

Substances

  • Adhesins, Bacterial
  • Antigens, CD
  • Bacterial Outer Membrane Proteins
  • CD66 antigens
  • Cell Adhesion Molecules
  • Receptors, Cell Surface
  • UspA protein, Moraxella catarrhalis
  • adhesin, Moraxella

Associated data

  • PDB/2QIH