Discovery and characterization of novel cyclotides originated from chimeric precursors consisting of Albumin-1 chain a and cyclotide domains in the Fabaceae family

The tropical plant Clitoria ternatea is a member of the Fabaceae family well known for its medicinal values. Heat extraction of C. ternatea revealed that the bioactive fractions contained heat-stable cysteine-rich peptides (CRPs). The CRP family of A1b (Albumin-1 chain b/leginsulins), which is a lin...

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Main Authors: Nguyen, Giang Kien Truc, Zhang, Sen, Nguyen, Ngan Thi Kim, Nguyen, Phuong Quoc Thuc, Chiu, Ming Sheau, Hardjojo, Antony, Tam, James P.
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2011
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Online Access:https://hdl.handle.net/10356/93943
http://hdl.handle.net/10220/7205
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-939432023-02-28T17:03:19Z Discovery and characterization of novel cyclotides originated from chimeric precursors consisting of Albumin-1 chain a and cyclotide domains in the Fabaceae family Nguyen, Giang Kien Truc Zhang, Sen Nguyen, Ngan Thi Kim Nguyen, Phuong Quoc Thuc Chiu, Ming Sheau Hardjojo, Antony Tam, James P. School of Biological Sciences DRNTU::Science::Biological sciences::Botany The tropical plant Clitoria ternatea is a member of the Fabaceae family well known for its medicinal values. Heat extraction of C. ternatea revealed that the bioactive fractions contained heat-stable cysteine-rich peptides (CRPs). The CRP family of A1b (Albumin-1 chain b/leginsulins), which is a linear cystine knot CRP, has been shown to present abundantly in the Fabaceae. In contrast, the cyclotide family, which also belongs to the cystine knot CRPs but with a cyclic structure, is commonly found in the Rubiaceae, Violaceae, and Cucurbitaceae families. In this study, we report the discovery of a panel of 15 heat-stable CRPs, of which 12 sequences (cliotide T1-T12) are novel. We show unambiguously that the cliotides are cyclotides and not A1bs, as determined by their sequence homology, disulfide connectivity, and membrane active properties indicated by their antimicrobial activities against Escherichia coli and cytotoxicities to HeLa cells. We also show that cliotides are prevalent in C. ternatea and are found in every plant tissue examined, including flowers, seeds, and nodules. In addition, we demonstrate that their precursors are chimeras, half from cyclotide and the other half from Albumin-1, with the cyclotide domain displacing the A1b domain in the precursor. Their chimeric structures likely originate from either horizontal gene transfer or convergent evolution in plant nuclear genomes, which are exceedingly rare events. Such atypical genetic arrangement also implies a different mechanism of biosynthetic processing of cyclotides in the Fabaceae and provides new understanding of their evolution in plants. Accepted version 2011-10-11T01:43:34Z 2019-12-06T18:48:15Z 2011-10-11T01:43:34Z 2019-12-06T18:48:15Z 2011 2011 Journal Article Nguyen, G. K. T., Zhang, S., Nguyen, N. T. K., Nguyen, P. Q. T., Chiu, M. S., Hardjojo, A. & Tam, J. P. (2011). Discovery and Characterization of Novel Cyclotides Originated from Chimeric Precursors Consisting of Albumin-1 Chain a and Cyclotide Domains in the Fabaceae Family. The Journal of Biological Chemistry, 286(27), 24275-24287. 0021-9258 https://hdl.handle.net/10356/93943 http://hdl.handle.net/10220/7205 10.1074/jbc.M111.229922 21596752 en The journal of biological chemistry © 2011 The American Society for Biochemistry and Molecular Biology. This is the author created version of a work that has been peer reviewed and accepted for publication by Discovery and Characterization of Novel Cyclotides Originated from Chimeric Precursors Consisting of Albumin-1 Chain a and Cyclotide Domains in the Fabaceae Family, JBC Papers in Press.  It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document.  The published version is available at: http://dx.doi.org/10.1074/jbc.M111.229922. 13 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences::Botany
spellingShingle DRNTU::Science::Biological sciences::Botany
Nguyen, Giang Kien Truc
Zhang, Sen
Nguyen, Ngan Thi Kim
Nguyen, Phuong Quoc Thuc
Chiu, Ming Sheau
Hardjojo, Antony
Tam, James P.
Discovery and characterization of novel cyclotides originated from chimeric precursors consisting of Albumin-1 chain a and cyclotide domains in the Fabaceae family
description The tropical plant Clitoria ternatea is a member of the Fabaceae family well known for its medicinal values. Heat extraction of C. ternatea revealed that the bioactive fractions contained heat-stable cysteine-rich peptides (CRPs). The CRP family of A1b (Albumin-1 chain b/leginsulins), which is a linear cystine knot CRP, has been shown to present abundantly in the Fabaceae. In contrast, the cyclotide family, which also belongs to the cystine knot CRPs but with a cyclic structure, is commonly found in the Rubiaceae, Violaceae, and Cucurbitaceae families. In this study, we report the discovery of a panel of 15 heat-stable CRPs, of which 12 sequences (cliotide T1-T12) are novel. We show unambiguously that the cliotides are cyclotides and not A1bs, as determined by their sequence homology, disulfide connectivity, and membrane active properties indicated by their antimicrobial activities against Escherichia coli and cytotoxicities to HeLa cells. We also show that cliotides are prevalent in C. ternatea and are found in every plant tissue examined, including flowers, seeds, and nodules. In addition, we demonstrate that their precursors are chimeras, half from cyclotide and the other half from Albumin-1, with the cyclotide domain displacing the A1b domain in the precursor. Their chimeric structures likely originate from either horizontal gene transfer or convergent evolution in plant nuclear genomes, which are exceedingly rare events. Such atypical genetic arrangement also implies a different mechanism of biosynthetic processing of cyclotides in the Fabaceae and provides new understanding of their evolution in plants.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Nguyen, Giang Kien Truc
Zhang, Sen
Nguyen, Ngan Thi Kim
Nguyen, Phuong Quoc Thuc
Chiu, Ming Sheau
Hardjojo, Antony
Tam, James P.
format Article
author Nguyen, Giang Kien Truc
Zhang, Sen
Nguyen, Ngan Thi Kim
Nguyen, Phuong Quoc Thuc
Chiu, Ming Sheau
Hardjojo, Antony
Tam, James P.
author_sort Nguyen, Giang Kien Truc
title Discovery and characterization of novel cyclotides originated from chimeric precursors consisting of Albumin-1 chain a and cyclotide domains in the Fabaceae family
title_short Discovery and characterization of novel cyclotides originated from chimeric precursors consisting of Albumin-1 chain a and cyclotide domains in the Fabaceae family
title_full Discovery and characterization of novel cyclotides originated from chimeric precursors consisting of Albumin-1 chain a and cyclotide domains in the Fabaceae family
title_fullStr Discovery and characterization of novel cyclotides originated from chimeric precursors consisting of Albumin-1 chain a and cyclotide domains in the Fabaceae family
title_full_unstemmed Discovery and characterization of novel cyclotides originated from chimeric precursors consisting of Albumin-1 chain a and cyclotide domains in the Fabaceae family
title_sort discovery and characterization of novel cyclotides originated from chimeric precursors consisting of albumin-1 chain a and cyclotide domains in the fabaceae family
publishDate 2011
url https://hdl.handle.net/10356/93943
http://hdl.handle.net/10220/7205
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