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 journalArticlepeer-review

    260 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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