title: The cyclotide family of circular miniproteins: nature's combinatorial peptide template.
abstract: The cyclotides are a recently discovered family of miniproteins that contain a head-to-tail cyclized backbone and a knotted arrangement of disulfide bonds. They are approximately 30 amino acids in size and are present in high abundance in plants from the Violaceae, Rubiaceae, and Cucurbitaceae families, with individual plants containing a suite of up to 100 cyclotides. They have a diverse range of biological activities, including uterotonic, anti-HIV, antitumor, and antimicrobial activities, although their natural function is likely that of defending their host plants from pathogens and pests. This review focuses on the structural aspects of cyclotides, which may be thought of as a natural combinatorial peptide template in which a wide range of amino acids is displayed on a compact molecular core made up of the cyclic cystine knot structural motif. Cyclotides are exceptionally stable and are resistant to denaturation via thermal, chemical, or enzymatic treatments. The structural features that contribute to their remarkable stability are described in this review.
authors.affiliation: Institute for Molecular Bioscience and Australian Research Council Special Research Centre for Functional and Applied Genomics, University of Queensland, Brisbane. d.craik@imb.uq.edu.au
authors.forename: David J
authors.initials: DJ
authors.lastname: Craik
authors.forename: Masa
authors.initials: M
authors.lastname: Cemazar
authors.forename: Conan K L
authors.initials: CK
authors.lastname: Wang
authors.forename: Norelle L
authors.initials: NL
authors.lastname: Daly
mesh_terms: D000595:Amino Acid Sequence; D020650:Combinatorial Chemistry Techniques; D017124:Conserved Sequence; D047169:Cyclotides / Q000737:chemistry*; D003545:Cysteine / Q000737:chemistry; D047168:Cystine Knot Motifs; D004220:Disulfides / Q000737:chemistry; D006358:Hot Temperature; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry*; D010940:Plant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013698:Templates, Genetic
chemical_list: D047169:Cyclotides; D004220:Disulfides; D010455:Peptides; D010940:Plant Proteins; D003545:Cysteine