Homology modelling of transferrin-binding protein A from Neisseria meningitidis

Jonathan S. Oakhill, Brian J. Sutton, Andrew R. Gorringe, Robert W. Evans*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


Neisseria meningitidis, a causative agent of bacterial meningitis, obtains transferrin-bound iron by expressing two outer membrane located transferrin-binding proteins, TbpA and TbpB. TbpA is thought to be an integral outer membrane pore that facilitates iron uptake. Evidence suggests that TbpA is a useful antigen for inclusion in a vaccine effective against meningococcal disease, hence the identification of regions involved in ligand binding is of paramount importance to design strategies to block uptake of iron. The protein shares sequence and functional similarities to the Escherichia coli siderophore receptors FepA and FhuA, whose structures have been determined. These receptors are composed of two domains, a 22-stranded β-barrel and an N-terminal plug region that sits within the barrel and occludes the transmembrane pore. A three-dimensional TbpA model was constructed using FepA and FhuA structural templates, hydrophobicity analysis and homology modelling. TbpA was found to possess a similar architecture to the siderophore receptors. In addition to providing insights into the highly immunogenic nature of TbpA and allowing the prediction of potentially important ligand-binding epitopes, the model also reveals a narrow channel through its entire length. The relevance of this channel and the spatial arrangement of external loops, to the mechanism of iron translocation employed by TbpA is discussed.

Original languageEnglish
Pages (from-to)221-228
Number of pages8
JournalProtein Engineering, Design and Selection
Issue number5
Publication statusPublished - May 2005

Bibliographical note

Funding Information:
J.S.O. was funded by an MRC Collaborative Studentship. Research at Health Protection Agency, Porton Down, was funded by the UK Department of Health.


  • Iron
  • Meningococcal
  • TbpA
  • Transferrin


Dive into the research topics of 'Homology modelling of transferrin-binding protein A from Neisseria meningitidis'. Together they form a unique fingerprint.

Cite this