Discovery of an unusual biosynthetic origin for circular proteins in legumes

Poth, Aaron G., Colgrave, Michelle L., Lyons, Russell E., Daly, Norelle L. and Craik, David J. (2011) Discovery of an unusual biosynthetic origin for circular proteins in legumes. Proceedings of the National Academy of Sciences of the United State of America, 108 25: 10127-10132. doi:10.1073/pnas.1103660108


Author Poth, Aaron G.
Colgrave, Michelle L.
Lyons, Russell E.
Daly, Norelle L.
Craik, David J.
Title Discovery of an unusual biosynthetic origin for circular proteins in legumes
Journal name Proceedings of the National Academy of Sciences of the United State of America   Check publisher's open access policy
ISSN 0027-8424
1091-6490
Publication date 2011-06-21
Sub-type Article (original research)
DOI 10.1073/pnas.1103660108
Volume 108
Issue 25
Start page 10127
End page 10132
Total pages 6
Place of publication Washington, DC, U.S.A.
Publisher National Academy of Sciences
Collection year 2012
Language eng
Formatted abstract
Cyclotides are plant-derived proteins that have a unique cyclic cystine knot topology and are remarkably stable. Their natural function is host defense, but they have a diverse range of pharmaceutically important activities, including uterotonic activity and anti-HIV activity, and have also attracted recent interest as templates in drug design. Here we report an unusual biosynthetic origin of a precursor protein of a cyclotide from the butterfly pea, Clitoria ternatea, a representative member of the Fabaceae plant family. Unlike all previously reported cyclotides, the domain corresponding to the mature cyclotide from this Fabaceae plant is embedded within an albumin precursor protein. We confirmed the expression and correct processing of the cyclotide encoded by the Cter M precursor gene transcript following extraction from C. ternatea leaf and sequencing by tandem mass spectrometry. The sequence was verified by direct chemical synthesis and the peptide was found to adopt a classic knotted cyclotide fold as determined by NMR spectroscopy. Seven additional cyclotide sequences were also identified from C. ternatea leaf and flower, five of which were unique. Cter M displayed insecticidal activity against the cotton budworm Helicoverpa armigera and bound to phospholipid membranes, suggesting its activity is modulated by membrane disruption. The Fabaceae is the third largest family of flowering plants and many Fabaceous plants are of huge significance for human nutrition. Knowledge of Fabaceae cyclotide gene transcripts should enable the production of modified cyclotides in crop plants for a variety of agricultural or pharmaceutical applications, including plant-produced designer peptide drugs.
Keyword Cyclic peptides
Structure
Cystine knot
Kalata B1
Cyclotide kalata B1
Cyclic cystine knot
Plant cyclotides
Insecticidal activity
Scanning mutagenesis
Structural motif
Peptides
Miniproteins
Bioactivity
Polypeptide
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
Institute for Molecular Bioscience - Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 51 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 13 Oct 2011, 17:05:12 EST by Professor David Craik on behalf of Institute for Molecular Bioscience