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Factors Influencing the Stability of Cyclotides: Proteins with a Circular Backbone and Cystine Knot Motif

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Abstract

Cyclotides are a large family of mini-proteins that have the distinguishing features of a head-to-tail cyclised backbone and a cystine knot formed by six conserved cysteine residues. They are present in plants from the Rubiaceae, Violaceae and Cucurbitaceae families. The unique structural features of the cyclotides make them extremely resistant to chemical, thermal and proteolytic degradation. In this article we review recent studies from our laboratory that dissect the role of the individual structural elements in defining the stability of cyclotides. The resistance of cyclotides to chemical and proteolytic degradation is in large part due to the cystine knot, whereas the thermal stability is a composite of several features including the cystine knot, the cyclic backbone and the hydrogen bonding network. A range of biological activities of cyclotides is critically dependent on the presence of the cyclic backbone.

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Acknowledgments

We thank colleagues from our laboratory who contributed to the studies listed in the references. Work in our laboratory is supported by grants from the Australian Research Council and the National Health and Medical Research Council. David Craik is an Australian Research Council Professorial Fellow. Maša Čemažar is an Australian Research Council Postdoctoral Fellow.

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Correspondence to David J Craik.

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Australian Peptide Conference Issue.

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Čemažar, M., Craik, D.J. Factors Influencing the Stability of Cyclotides: Proteins with a Circular Backbone and Cystine Knot Motif. Int J Pept Res Ther 12, 253–260 (2006). https://doi.org/10.1007/s10989-006-9019-2

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  • DOI: https://doi.org/10.1007/s10989-006-9019-2

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