Local and long-range stability in tandemly arrayed tetratricopeptide repeats

Main, Ewan R G, Stott, Katherine, Jackson, Sophie E and Regan, Lynne (2005) Local and long-range stability in tandemly arrayed tetratricopeptide repeats. Proceedings of the National Academy of Sciences, 102 (16). pp. 5721-5726. ISSN 0027-8424

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Abstract

The tetratricopeptide repeat (TPR) is a 34-aa alpha-helical motif that occurs in tandem arrays in a variety of different proteins. In natural proteins, the number of TPR motifs ranges from 3 to 16 or more. These arrays function as molecular scaffolds and frequently mediate protein-protein interactions. We have shown that correctly folded TPR domain proteins, exhibiting the typical helix-turn-helix fold, can be designed by arraying tandem repeats of an idealized TPR consensus motif. To date, three designed proteins, CTPR1, CTPR2, and CTPR3 (consensus TPR number of repeats) have been characterized. Their high-resolution crystal structures show that the designed proteins indeed adopt the typical TPR fold, which is specified by the correct positioning of key residues. Here, we present a study of the thermodynamic properties and folding kinetics of this set of designed proteins. Chemical denaturation, monitored by CD and fluorescence, was used to assess the folding and global stability of each protein. NMR-detected amide proton exchange was used to investigate the stability of each construct at a residue-specific level. The results of these studies reveal a stable core, which defines the intrinsic stability of an individual TPR motif. The results also show the relationship between the number of tandem repeats and the overall stability and folding of the protein

Item Type: Article
Additional Information: ERGM was first author (designed, performed, analyzed and wrote the majority of the work). The paper describes one of the first biophysical studies on repeat proteins (how stability / folding changes on increasing protein size). The research has been presented at a number of international conferences.
Schools and Departments: School of Life Sciences > Chemistry
Depositing User: Ewan Main
Date Deposited: 06 Feb 2012 19:10
Last Modified: 21 May 2012 13:18
URI: http://sro.sussex.ac.uk/id/eprint/19464
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