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Title: Structural stability and the folding pathway of a series of consensus tetratricopeptide repeat proteins
Author: Javadi, Yalda
ISNI:       0000 0004 2680 9836
Awarding Body: University of Sussex
Current Institution: University of Sussex
Date of Award: 2009
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Repeat proteins contain short, tandem array of simple structural motifs that stack together to form elongated structures, which are stabilised by 'local' interactions from residues close in primary sequence. Their recurring modular and highly symmetrical structure, which is very different from globular proteins, makes extremely attractive targets for studying protein folding. One example is the ubiquitous tetratricopeptide repeat (TPR) protein, a thirty-four amino acid helix-turn-helix motif. In this thesis biophysical techniques are used to characterise a series of the deigned consensus variant of this protein (CTPRa), which range from two to ten-repeats (86 to 358 amino acid residues). In particular, the energy landscapes of the CTPRa proteins are explored in terms of equilibrium stability and un/folding kinetics as identical repeating units are added. The data reveal that the repetitive and modular nature of the CTPRa proteins is reflected in their equilibrium stability. In particular, they are best described by the one-dimensional Ising model, which assumes nearest neighbour coupling of the repeats. Furthermore, the thermodynamic behaviour of the CTPRa series is reiterated in their folding pathway. With the exception of CTPRa2, which folds cooperatively, on-pathway intermediates are populated with increasing repeat number. This corresponds to an increasingly complex landscape that culminates in a misfolded intermediate that is populated when the CTPRa motif has at least 10 repeats. These novel results extend current understanding of the malleable folding pathway of repeat proteins as well as demonstrating the impact that the addition of identical repeats has on the energy landscape.
Supervisor: Not available Sponsor: Not available
Qualification Name: Not available Qualification Level: Doctoral
EThOS ID:  DOI: Not available