Molecular features governing the stability and specificity of functional complex formation by Mycobacterium tuberculosis CFP-10/ESAT-6 family proteins

Lightbody, Kirsty L. and Ilghari, Dariush and Waters, Lorna C. and Carey, Gemma and Bailey, Mark A. and Williamson, Richard A. and Renshaw, Philip S. and Carr, Mark D. (2008) Molecular features governing the stability and specificity of functional complex formation by Mycobacterium tuberculosis CFP-10/ESAT-6 family proteins. Journal of Biological Chemistry, 283 (25). pp. 17681-17690. ISSN 0021-9258. (The full text of this publication is not available from this repository)

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Official URL
http://dx.doi.org/10.1074/jbc.M800123200

Abstract

The Mycobacterium tuberculosis complex CFP-10/ESAT-6 family proteins play essential but poorly defined roles in tuberculosis pathogenesis. In this article we report the results of detailed spectroscopic studies of several members of the CFP10/ESAT-6 family. This work shows that the CFP-10/ESAT-6 related proteins, Rv0287 and Rv0288, form a tight 1:1 complex, which is predominantly helical in structure and is predicted to closely resemble the complex formed by CFP-10 and ESAT-6. In addition, the Rv0287.Rv0288 complex was found to be significantly more stable to both chemical and temperature induced denaturation than CFP-10.ESAT-6. This approach demonstrated that neither Rv0287.Rv0288 nor the CFP-10.ESAT-6 complexes are destabilized at low pH (4.5), indicating that even in low pH environments, such as the mature phagosome, both Rv0287.Rv0288 and CFP-10.ESAT-6 undoubtedly function as complexes rather than individual proteins. Analysis of the structure of the CFP-10.ESAT-6 complex and optimized amino acid sequence alignments of M. tuberculosis CFP-10/ESAT-6 family proteins revealed that residues involved in the intramolecular contacts between helices are conserved across the CFP-10/ ESAT-6 family, but not those involved in primarily intermolecular contacts. This analysis identified the molecular basis for the specificity and stability of complex formation between CFP-10/ ESAT-6 family proteins, and indicates that the formation of functional complexes with key roles in pathogenesis will be limited to genome partners, or very closely related family members, such as Rv0287/Rv0288 and Rv3019c/Rv3020c.

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: Jane Griffiths
Date Deposited: 19 Mar 2009 14:11
Last Modified: 17 Apr 2014 10:31
Resource URI: http://kar.kent.ac.uk/id/eprint/15775 (The current URI for this page, for reference purposes)
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