Exploring the folding energy landscape of a series of designed consensus tetratricopeptide repeat proteins

Javadi, Yalda and Main, Ewan (2009) Exploring the folding energy landscape of a series of designed consensus tetratricopeptide repeat proteins. Proceedings of the National Academy of Sciences, 106 (41). pp. 17383-17388. ISSN 1091-6490

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Abstract

Repeat proteins contain short, tandem arrays of simple structural motifs (20 to 40 amino acids). These stack together to form non-globular structures that are stabilised by short range interactions from residues close in primary sequence. Unlike globular proteins, they have few, if any, long range non-local stabilising interactions. One ubiquitous repeat is the tetratricopeptide motif (TPR) a 34 amino acid helix-turn-helix motif. In this article we describe the folding kinetics of a series of seven designed TPR proteins that are assembled from arraying identical designed consensus repeats (CTPRan). These range from the smallest two-repeat protein to a large ten-repeat protein ( 350 a.a). In particular, we investigate how the energy landscape changes with the addition of repeat units. The data reveal that although the CTPRa proteins have low local frustration, their highly symmetric, modular native structure is reflected in their multi-state kinetics of unfolding and folding. Moreover, although the initial folding of all CTPRan proteins involves a nucleus of similar solvent accessibility, their consequent steps to native structure change as repeat number increases. This corresponds to an increasingly complex landscape that culminates in CTPRa10 populating a misfolded, thus off-pathway, intermediate. These novel results extend our current understanding of the malleable folding pathways of repeat proteins and highlight the consequences of adding identical repeats to the energy landscape.

Item Type: Article
Schools and Departments: School of Life Sciences > Chemistry
Depositing User: Yalda Javadi
Date Deposited: 30 May 2012 11:05
Last Modified: 30 May 2012 11:05
URI: http://sro.sussex.ac.uk/id/eprint/30555
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