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.
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Authors | 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 |
Journal | The EMBO journal
(EMBO J)
Vol. 24
Issue 14
Pg. 2491-8
(Jul 20 2005)
ISSN: 0261-4189 [Print] England |
PMID | 15973432
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, Bacterial
- Bacterial Proteins
- CFP-10 protein, Mycobacterium tuberculosis
- ESAT-6 protein, Mycobacterium tuberculosis
- Virulence Factors
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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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