Structure and function of the complex formed by the tuberculosis virulence factors CFP-10 and ESAT-6

Philip S Renshaw, Kirsty L Lightbody, Vaclav Veverka, Fred W Muskett, Geoff Kelly, Thomas A Frenkiel, Stephen V Gordon, R Glyn Hewinson, Bernard Burke, Jim Norman, Richard A Williamson, Mark D Carr

Research output: Contribution to journalArticle

197 Citations (Scopus)

Abstract

The secreted Mycobacterium tuberculosis complex proteins CFP-10 and ESAT-6 have recently been shown to play an essential role in tuberculosis pathogenesis. We have determined the solution structure of the tight, 1:1 complex formed by CFP-10 and ESAT-6, and employed fluorescence microscopy to demonstrate specific binding of the complex to the surface of macrophage and monocyte cells. A striking feature of the complex is the long flexible arm formed by the C-terminus of CFP-10, which was found to be essential for binding to the surface of cells. The surface features of the CFP-10.ESAT-6 complex, together with observed binding to specific host cells, strongly suggest a key signalling role for the complex, in which binding to cell surface receptors leads to modulation of host cell behaviour to the advantage of the pathogen.

Original languageEnglish
Pages (from-to)2491-2498
Number of pages8
JournalThe EMBO journal
Volume24
Issue number14
DOIs
Publication statusPublished - 20 Jul 2005

Keywords

  • Amino Acid Sequence
  • Animals
  • Antigens, Bacterial/chemistry
  • Bacterial Proteins/chemistry
  • COS Cells
  • Cell Lineage
  • Cell Membrane/metabolism
  • Cells, Cultured
  • Cercopithecus aethiops
  • Humans
  • Mice
  • Molecular Sequence Data
  • Monocytes/metabolism
  • NIH 3T3 Cells
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Binding
  • Protein Structure, Tertiary
  • Signal Transduction/physiology
  • Structure-Activity Relationship
  • U937 Cells
  • Virulence Factors/chemistry

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    Renshaw, P. S., Lightbody, K. L., Veverka, V., Muskett, F. W., Kelly, G., Frenkiel, T. A., ... Carr, M. D. (2005). Structure and function of the complex formed by the tuberculosis virulence factors CFP-10 and ESAT-6. The EMBO journal, 24(14), 2491-2498. https://doi.org/10.1038/sj.emboj.7600732