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^*

^*Corresponding author for this work

Bovine TB, diseases and control

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

254 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	EMBO Journal
Volume	24
Issue number	14
Early online date	23 May 2005
DOIs	https://doi.org/10.1038/sj.emboj.7600732
Publication status	Published - 20 Jul 2005

Keywords

CFP-10
ESAT-6
Pathogenesis
Tuberculosis
Virulence

UN SDGs

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

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title = "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.",

keywords = "CFP-10, ESAT-6, Pathogenesis, Tuberculosis, Virulence",

author = "Renshaw, {Philip S.} and Lightbody, {Kirsty L.} and Vaclav Veverka and Muskett, {Fred W.} and Geoff Kelly and Frenkiel, {Thomas A.} and Gordon, {Stephen V.} and Hewinson, {R. Glyn} and Bernard Burke and Jim Norman and Williamson, {Richard A.} and Carr, {Mark D.}",

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T1 - Structure and function of the complex formed by the tuberculosis virulence factors CFP-10 and ESAT-6

AU - Renshaw, Philip S.

AU - Lightbody, Kirsty L.

AU - Veverka, Vaclav

AU - Muskett, Fred W.

AU - Kelly, Geoff

AU - Frenkiel, Thomas A.

AU - Gordon, Stephen V.

AU - Hewinson, R. Glyn

AU - Burke, Bernard

AU - Norman, Jim

AU - Williamson, Richard A.

AU - Carr, Mark D.

PY - 2005/7/20

Y1 - 2005/7/20

N2 - 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.

AB - 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.

KW - CFP-10

KW - ESAT-6

KW - Pathogenesis

KW - Tuberculosis

KW - Virulence

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JO - EMBO Journal

JF - EMBO Journal

IS - 14

ER -

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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