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Computational survey of peptides derived from disulphide-bonded protein loops that may serve as mediators of protein-protein interactions.

Version 2 2022-02-24, 15:16
Version 1 2019-11-23, 12:12
journal contribution
posted on 2022-02-24, 15:16 authored by Fergal J. Duffy, Marc DevocelleMarc Devocelle, David R. Croucher, Denis C. Shields

BACKGROUND: Bioactive cyclic peptides derived from natural sources are well studied, particularly those derived from non-ribosomal synthetases in fungi or bacteria. Ribosomally synthesised bioactive disulphide-bonded loops represent a large, naturally enriched library of potential bioactive compounds, worthy of systematic investigation.

RESULTS: We examined the distribution of short cyclic loops on the surface of a large number of proteins, especially membrane or extracellular proteins. Available three-dimensional structures highlighted a number of disulphide-bonded loops responsible for the majority of the likely binding interactions in a variety of protein complexes, due to their location at protein-protein interfaces. We find that disulphide-bonded loops at protein-protein interfaces may, but do not necessarily, show biological activity independent of their parent protein. Examining the conservation of short disulphide bonded loops in proteins, we find a small but significant increase in conservation inside these loops compared to surrounding residues. We identify a subset of these loops that exhibit a high relative conservation, particularly among peptide hormones.

CONCLUSIONS: We conclude that short disulphide-bonded loops are found in a wide variety of biological interactions. They may retain biological activity outside their parent proteins. Such structurally independent peptides may be useful as biologically active templates for the development of novel modulators of protein-protein interactions.

Funding

Science Foundation Ireland

History

Comments

The original article is available at www.biomedcentral.com

Published Citation

Duffy FJ, Devocelle M, Croucher DR, Shields DC. Computational survey of peptides derived from disulphide-bonded protein loops that may serve as mediators of protein-protein interactions. BMC Bioinformatics. 2014;15:305.

Publication Date

2014-09-17

PubMed ID

25231912

Department/Unit

  • Chemistry

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