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

Singh, Birendra LU ; Tamim, Al-Jubair LU ; Thunnissen, Marjolein LU ; Mörgelin, Matthias LU and Riesbeck, Kristian LU (2013) In Infection and Immunity 81(3). p.801-814
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Infection and Immunity
volume
81
issue
3
pages
801 - 814
publisher
American Society for Microbiology
external identifiers
  • wos:000316313200021
  • pmid:23275089
  • scopus:84874751330
ISSN
1098-5522
DOI
10.1128/IAI.01111-12
language
English
LU publication?
yes
id
3595892e-05e3-4bf6-914c-ecadccb22d48 (old id 3439144)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23275089?dopt=Abstract
date added to LUP
2013-02-04 09:40:39
date last changed
2019-02-20 02:47:40
@article{3595892e-05e3-4bf6-914c-ecadccb22d48,
  abstract     = {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.},
  author       = {Singh, Birendra and Tamim, Al-Jubair and Thunnissen, Marjolein and Mörgelin, Matthias and Riesbeck, Kristian},
  issn         = {1098-5522},
  language     = {eng},
  number       = {3},
  pages        = {801--814},
  publisher    = {American Society for Microbiology},
  series       = {Infection and Immunity},
  title        = {The unique structure of Haemophilus influenzae protein E reveals multiple binding sites for host factors.},
  url          = {http://dx.doi.org/10.1128/IAI.01111-12},
  volume       = {81},
  year         = {2013},
}