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

doi:10.1038/sj.emboj.7600732

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

School of Life Sciences

Research output: Contribution to journal › Article › peer-review

235 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 language	English
Pages (from-to)	2491-2498
Number of pages	8
Journal	The EMBO journal
Volume	24
Issue number	14
DOIs	https://doi.org/10.1038/sj.emboj.7600732
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/sj.emboj.7600732

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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 journal › Article › peer-review

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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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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KW - Mice

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

Abstract

Keywords

UN SDGs

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