title: Processing of a 22 kDa precursor protein to produce the circular protein tricyclon A.
abstract: Cyclotides are a family of plant proteins that have the unusual combination of head-to-tail backbone cyclization and a cystine knot motif. They are exceptionally stable and show resistance to most chemical, physical, and enzymatic treatments. The structure of tricyclon A, a previously unreported cyclotide, is described here. In this structure, a loop that is disordered in other cyclotides forms a beta sheet that protrudes from the globular core. This study indicates that the cyclotide fold is amenable to the introduction of a range of structural elements without affecting the cystine knot core of the protein, which is essential for the stability of the cyclotides. Tricyclon A does not possess a hydrophobic patch, typical of other cyclotides, and has minimal hemolytic activity, making it suitable for pharmaceutical applications. The 22 kDa precursor protein of tricyclon A was identified and provides clues to the processing of these fascinating miniproteins.
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Mulvenna
authors.forename: Lillian
authors.initials: L
authors.lastname: Sando
authors.forename: David J
authors.initials: DJ
authors.lastname: Craik
mesh_terms: D000595:Amino Acid Sequence; D047169:Cyclotides / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis; D006801:Humans; D008969:Molecular Sequence Data; D032067:Oldenlandia / Q000378:metabolism; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D010940:Plant Proteins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011487:Protein Conformation; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D047169:Cyclotides; D010456:Peptides, Cyclic; D010940:Plant Proteins; D011498:Protein Precursors