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Distribution and Evolution of Circular Miniproteins in Flowering Plants^[W]

^a Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia
^b Department of General Biology/Botany, Institute of Biological Sciences, Federal University of Goiás, 74001-970 Goiânia, Goiás, Brazil
^c National Botanic Garden of Belgium, Domein van Bouchout, BE-1860, Meise, Belgium
^d Department of Medicinal Chemistry, Division of Pharmacognosy, Uppsala University, Biomedical Centre, 751 23 Uppsala, Sweden

⁴ Address correspondence to d.craik{at}imb.uq.edu.au.

Cyclotides are disulfide-rich miniproteins with the unique structural features of a circular backbone and knotted arrangement of three conserved disulfide bonds. Cyclotides have been found only in two plant families: in every analyzed species of the violet family (Violaceae) and in few species of the coffee family (Rubiaceae). In this study, we analyzed >200 Rubiaceae species and confirmed the presence of cyclotides in 22 species. Additionally, we analyzed >140 species in related plant families to Rubiaceae and Violaceae and report the occurrence of cyclotides in the Apocynaceae. We further report new cyclotide sequences that provide insights into the mechanistic basis of cyclotide evolution. On the basis of the phylogeny of cyclotide-bearing plants and the analysis of cyclotide precursor gene sequences, we hypothesize that cyclotide evolution occurred independently in various plant families after the divergence of Asterids and Rosids (125 million years ago). This is strongly supported by recent findings on the in planta biosynthesis of cyclotides, which involves the serendipitous recruitment of ubiquitous proteolytic enzymes for cyclization. We further predict that the number of cyclotides within the Rubiaceae may exceed tens of thousands, potentially making cyclotides one of the largest protein families in the plant kingdom.

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Cyclotides: Cyclical Miniproteins with a Cystine Knot Configuration

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Plant Cell 2008 20: 2285. [Full Text]  

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