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

University of Leicester

Research output: Contribution to journal › Article › peer-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 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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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.",

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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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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

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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.

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KW - Animals

KW - Antigens, Bacterial/chemistry

KW - Bacterial Proteins/chemistry

KW - COS Cells

KW - Cell Lineage

KW - Cell Membrane/metabolism

KW - Cells, Cultured

KW - Cercopithecus aethiops

KW - Humans

KW - Mice

KW - Molecular Sequence Data

KW - Monocytes/metabolism

KW - NIH 3T3 Cells

KW - Nuclear Magnetic Resonance, Biomolecular

KW - Protein Binding

KW - Protein Structure, Tertiary

KW - Signal Transduction/physiology

KW - Structure-Activity Relationship

KW - U937 Cells

KW - Virulence Factors/chemistry

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DO - 10.1038/sj.emboj.7600732

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SN - 0261-4189

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JO - The EMBO journal

JF - The 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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