The Evolution of Momordica Cyclic Peptides

T. Mahatmanto, Josh Mylne, A.G. Poth, J. Swedberg, Q. Kaas, H. Schaefer, D.J. Craik

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Cyclic proteins have evolved for millions of years across all kingdoms of life to confer structural stability over their acyclic counterparts while maintaining intrinsic functional properties. Here, we show that cyclic miniproteins (or peptides) from Momordica (Cucurbitaceae) seeds evolved in species that diverged from an African ancestor around 19 Ma. The ability to achieve head-to-tail cyclization of Momordica cyclic peptides appears to have been acquired through a series of mutations in their acyclic precursor coding sequences following recent and independent gene expansion event(s). Evolutionary analysis of Momordica cyclic peptides reveals sites that are under selection, highlighting residues that are presumably constrained for maintaining their function as potent trypsin inhibitors. Molecular dynamics of Momordica cyclic peptides in complex with trypsin reveals site-specific residues involved in target binding. In a broader context, this study provides a basis for selecting Momordica species to further investigate the biosynthesis of the cyclic peptides and for constructing libraries that may be screened against evolutionarily related serine proteases implicated in human diseases.
Original languageEnglish
Pages (from-to)392-405
JournalMolecular Biology and Evolution
Volume32
Issue number2
DOIs
Publication statusPublished - 2 Feb 2015

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Momordica
cyclic peptides
Cyclic Peptides
peptide
Cucurbitaceae
Peptide Library
Trypsin Inhibitors
molecular dynamics
Serine Proteases
serine proteinases
trypsin inhibitors
Cyclization
Molecular Dynamics Simulation
human diseases
ancestry
Trypsin
trypsin
functional properties
inhibitor
mutation

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Mahatmanto, T., Mylne, J., Poth, A. G., Swedberg, J., Kaas, Q., Schaefer, H., & Craik, D. J. (2015). The Evolution of Momordica Cyclic Peptides. Molecular Biology and Evolution, 32(2), 392-405. https://doi.org/10.1093/molbev/msu307
Mahatmanto, T. ; Mylne, Josh ; Poth, A.G. ; Swedberg, J. ; Kaas, Q. ; Schaefer, H. ; Craik, D.J. / The Evolution of Momordica Cyclic Peptides. In: Molecular Biology and Evolution. 2015 ; Vol. 32, No. 2. pp. 392-405.
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Mahatmanto, T, Mylne, J, Poth, AG, Swedberg, J, Kaas, Q, Schaefer, H & Craik, DJ 2015, 'The Evolution of Momordica Cyclic Peptides' Molecular Biology and Evolution, vol. 32, no. 2, pp. 392-405. https://doi.org/10.1093/molbev/msu307

The Evolution of Momordica Cyclic Peptides. / Mahatmanto, T.; Mylne, Josh; Poth, A.G.; Swedberg, J.; Kaas, Q.; Schaefer, H.; Craik, D.J.

In: Molecular Biology and Evolution, Vol. 32, No. 2, 02.02.2015, p. 392-405.

Research output: Contribution to journalArticle

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Mahatmanto T, Mylne J, Poth AG, Swedberg J, Kaas Q, Schaefer H et al. The Evolution of Momordica Cyclic Peptides. Molecular Biology and Evolution. 2015 Feb 2;32(2):392-405. https://doi.org/10.1093/molbev/msu307