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

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.
AuthorsPhilip 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
JournalThe EMBO journal (EMBO J) Vol. 24 Issue 14 Pg. 2491-8 (Jul 20 2005) ISSN: 0261-4189 [Print] England
PMID15973432 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, Bacterial
  • Bacterial Proteins
  • CFP-10 protein, Mycobacterium tuberculosis
  • ESAT-6 protein, Mycobacterium tuberculosis
  • Virulence Factors
Topics
  • Amino Acid Sequence
  • Animals
  • Antigens, Bacterial (chemistry, metabolism, physiology)
  • Bacterial Proteins (chemistry, metabolism, physiology)
  • COS Cells
  • Cell Lineage
  • Cell Membrane (metabolism)
  • Cells, Cultured
  • Chlorocebus 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, physiology)

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