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

187 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

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Virulence Factors
Tuberculosis
Macrophages
Fluorescence microscopy
Cell Surface Receptors
Pathogens
Fluorescence Microscopy
Modulation
Monocytes
Proteins

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

Cite this

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

Structure and function of the complex formed by the tuberculosis virulence factors CFP-10 and ESAT-6. / Renshaw, Philip S; Lightbody, Kirsty L; Veverka, Vaclav; Muskett, Fred W; Kelly, Geoff; Frenkiel, Thomas A; Gordon, Stephen V; Hewinson, R Glyn; Burke, Bernard; Norman, Jim; Williamson, Richard A; Carr, Mark D.

In: The EMBO journal, Vol. 24, No. 14, 20.07.2005, p. 2491-2498.

Research output: Contribution to journalArticle

Renshaw, PS, Lightbody, KL, Veverka, V, Muskett, FW, Kelly, G, Frenkiel, TA, Gordon, SV, Hewinson, RG, Burke, B, Norman, J, Williamson, RA & Carr, MD 2005, 'Structure and function of the complex formed by the tuberculosis virulence factors CFP-10 and ESAT-6' The EMBO journal, vol. 24, no. 14, pp. 2491-2498. https://doi.org/10.1038/sj.emboj.7600732
Renshaw PS, Lightbody KL, Veverka V, Muskett FW, Kelly G, Frenkiel TA et al. Structure and function of the complex formed by the tuberculosis virulence factors CFP-10 and ESAT-6. The EMBO journal. 2005 Jul 20;24(14):2491-2498. https://doi.org/10.1038/sj.emboj.7600732
Renshaw, Philip S ; Lightbody, Kirsty L ; Veverka, Vaclav ; Muskett, Fred W ; Kelly, Geoff ; Frenkiel, Thomas A ; Gordon, Stephen V ; Hewinson, R Glyn ; Burke, Bernard ; Norman, Jim ; Williamson, Richard A ; Carr, Mark D. / Structure and function of the complex formed by the tuberculosis virulence factors CFP-10 and ESAT-6. In: The EMBO journal. 2005 ; Vol. 24, No. 14. pp. 2491-2498.
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