Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.432988
Title: Characterisation of the binding specificity and functional roles of Mycobacterium tuberculosis complex CFP-10/ESAT-6 family proteins
Author: Lightbody, Kirsty Lynn
ISNI:       0000 0001 3609 9151
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2006
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Abstract:
The secreted Mycobacterium tuberculosis complex proteins CFP-10 and ESAT-6 form a tight, 1:1 heterodimeric complex which is known to play an essential, but as yet undefined, role in tuberculosis pathogenesis. CFP-10 and ESAT-6 are members of a large protein family, including 23 members within the M. tuberculosis genome. Like CFP-10 and ESAT-6 the majority of family members are located in pairs within the genome. Yeast two-hybrid studies reported here show that the genome partners Rv0287/Rv0288 and Rv3019c/Rv3020c also form heterodimeric complexes, suggesting that all genome pairs within the CFP-10/ESAT-6 family are likely to form complexes. Further yeast two-hybrid analysis also revealed that closely related pairs, such as Rv0287/Rv0288 and Rv3019c/Rv3020c are able to bind to non-genome partners, however, distantly related proteins, including CFP-10 and ESAT-6, are unlikely to form complexes with family members other than their genome partner. The ability of some CFP-10/ESAT-6 family proteins to form complexes with non-genome partners greatly increases the number of potential complexes, and may have a significant effect on the functional diversity of this important protein family. The recently determined structure of the CFP-10˙ESAT-6 complex reveals that both proteins adopt an elongated helix-turn-helix hairpin structure and lie antiparallel to each other to form a stable four helix bundle. The surface and structural features of the complex suggest a role in binding one or more target proteins. fluorescence microscopy studies described here have demonstrated specific binding of the CFP-10˙ESAT-6 complex to the surface of monocyte and macrophage cells, suggesting the presence of a specific receptor on host cells and a possible cell role in pathogen-host cell signalling. A striking feature of the complex is the flexible C-terminal region of CFP-10, which was found to be essential for binding to host cells.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.432988  DOI: Not available
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