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    Context-dependent energetics of loop extensions in a family of tandem-repeat proteins

    Perez-RIba, A. and Lowe, Alan R. and Main, E.R.G. and Itzhaki, L.S. (2018) Context-dependent energetics of loop extensions in a family of tandem-repeat proteins. Biophysical Journal 114 (11), pp. 2552-2562. ISSN 0006-3495.

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    Consensus-designed tetratricopeptide repeat proteins are highly stable, modular proteins that are strikingly amenable to rational engineering. They therefore have tremendous potential as building blocks for biomaterials and biomedicine. Here, we explore the possibility of extending the loops between repeats to enable further diversification, and we investigate how this modification affects stability and folding cooperativity. We find that extending a single loop by up to 25 residues does not disrupt the overall protein structure, but, strikingly, the effect on stability is highly context-dependent: in a two-repeat array, destabilization is relatively small and can be accounted for purely in entropic terms, whereas extending a loop in the middle of a large array is much more costly because of weakening of the interaction between the repeats. Our findings provide important and, to our knowledge, new insights that increase our understanding of the structure, folding, and function of natural repeat proteins and the design of artificial repeat proteins in biotechnology.


    Item Type: Article
    School: School of Science > Biological Sciences
    Research Centres and Institutes: Structural Molecular Biology, Institute of (ISMB)
    Depositing User: Alan Lowe
    Date Deposited: 27 Apr 2018 08:34
    Last Modified: 17 Jun 2021 14:41


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