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The unique structure of Haemophilus influenzae protein E reveals multiple binding sites for host factors.

In English

Författare

Summary, in English

Haemophilus influenzae protein E (PE) is a multifunctional adhesin, involved in direct interactions with lung epithelial cells and host proteins, including plasminogen and the extracellular matrix proteins vitronectin and laminin. We recently crystallized PE and successfully collected X-ray diffraction data to 1.8 Å. Here we solved the structure of a recombinant version of PE and analyzed different functional regions. It is a dimer in solution and in the asymmetric unit of the crystals. The dimer has a structure that resembles a flattened β-barrel. It is however not a true β-barrel as there are differences in both the hydrogen bonding pattern and the shape. Each monomer consisted of a 6-stranded antiparallel β-sheet with a rigid α-helix at the C-terminal tethered to the concave side of the sheet by a disulfide bridge. The laminin/plasminogen binding region (residues 41-68) is exposed, while the vitronectin binding region (residues 84-108) is partially accessible in the dimer. The dimerized PE explains the simultaneous interaction with laminin and vitronectin. In addition, we found this unique adhesin being present in many bacterial genera of the family Pasteurallaceae and also orthologues in other unrelated species (Enterobacter cloacae and Listeria monocytogenes). Peptides corresponding to the surface-exposed regions PE24-37, PE74-89, and PE134-156 were immunogenic in the mouse. Importantly, these peptide-based antibodies also recognised PE at the bacterial surface. Taken together, our detailed structure of PE explains how this important virulence factor of H. influenzae simultaneously interacts with host vitronectin, laminin or plasminogen promoting bacterial pathogenesis.

Publiceringsår

2013

Språk

Engelska

Sidor

801-814

Publikation/Tidskrift/Serie

Infection and Immunity

Volym

81

Issue

3

Dokumenttyp

Artikel i tidskrift

Förlag

American Society for Microbiology

Ämne

  • Microbiology in the medical area
  • Infectious Medicine

Status

Published

Forskningsgrupp

  • Clinical Microbiology, Malmö

ISBN/ISSN/Övrigt

  • ISSN: 1098-5522