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J. Biol. Chem., Vol. 277, Issue 24, 21598-21603, June 14, 2002
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From the The proteins ESAT-6 and CFP-10 have been shown to
be secreted by Mycobacterium tuberculosis and
Mycobacterium bovis cells, to be potent T-cell antigens,
and to have a clear but as yet undefined role in tuberculosis
pathogenesis. We have successfully overexpressed both ESAT-6 and CFP-10
in Escherichia coli and developed efficient purification
schemes. Under in vivo-like conditions, a combination of
fluorescence, circular dichroism, and nuclear magnetic resonance spectroscopy have shown that ESAT-6 contains up to 75% helical secondary structure, but little if any stable tertiary structure, and
exists in a molten globule-like state. In contrast, CFP-10 was found to
form an unstructured, random coil polypeptide. An exciting discovery
was that ESAT-6 and CFP-10 form a tight, 1:1 complex, in which both
proteins adopt a fully folded structure, with about two-thirds of the
backbone in a regular helical conformation. This clearly suggests that
ESAT-6 and CFP-10 are active as the complex and raises the interesting
question of whether other ESAT-6/CFP-10 family proteins (22 paired
genes in M. tuberculosis) also form tight, 1:1 complexes,
and if so, is this limited to their genome partner, or is there scope
for wider interactions within the protein family, which could provide
greater functional flexibility?
Conclusive Evidence That the Major T-cell Antigens of the
Mycobacterium tuberculosis Complex ESAT-6 and CFP-10
Form a Tight, 1:1 Complex and Characterization of the Structural
Properties of ESAT-6, CFP-10, and the ESAT-6·CFP-10
Complex
IMPLICATIONS FOR PATHOGENESIS AND VIRULENCE*
,
Department of Biochemistry, University of
Leicester, Adrian Building, University Road, Leicester LE1 7RH,
§ Department of Biosciences, University of Kent, Canterbury,
Kent CT2 7NJ, and ¶ TB Research Group, Department of Bacterial
Diseases, Veterinary Laboratories Agency Weybridge, New Haw,
Addlestone, Surrey KT15 3NB, United Kingdom
*
This work was supported in part by Grants 047795 and 055394 from the Wellcome Trust, by the award of a Biotechnology and Biological Sciences Research Council studentship (to P. S. R.), and by the Veterinary Laboratories Agency, United Kingdom. M. C. is one of the
principle investigators of the M. tuberculosis Structural Genomics Consortium, which is supported by the National Institutes of
Health and by the United States Department of Energy.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.:
44-116-252-3054; Fax: 44-116-223-1503; E-mail: mdc12@le.ac.uk.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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