orals 5th Asia-Pacific NMR Symposium 2013

Structural diversity of a novel family of cyclic plant peptides (#24)

Bastian Franke 1 , Alysha G. Elliott 2 , Joshua S. Mylne 2 3 , K. Johan Rosengren 1
  1. School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia
  2. The University of Queensland, Institute for Molecular Bioscience, Brisbane, QLD, Australia
  3. School of Chemistry and Biochemistry & ARC Centre of Excellence in Plant Energy Biology, The University of Western Australia, Perth, WA, Australia

Sunflower trypsin inhibitor-1 (SFTI-1) is a 14-residue cyclic peptide isolated from the seeds of sunflower (Helianthus annuus). It is characterized by potent inhibition of trypsin and a highly stable fold due to its cyclic backbone and a cross-bracing disulfide. SFTI-1 has potential applications as a promising drug lead and protein engineering framework. The origin of SFTI-1 is intriguing. It is produced from a precursor for an albumin seed storage protein named PawS1, and is cleaved out and head-to-tail cyclized during the processing of the albumin by a Cys-protease asparaginyl endopeptidase. SFTI-1 shows structural, functional and sequence similarities to the trypsin inhibitory loop of Bowman Birk Inhibitors, but appears to have evolved independently. Based on liquid chromatography mass spectrometry and a gene-based screening approach of an additional 273 species in the family Asteraceae we have found evidence for a number of cyclic and acyclic peptides, showing striking structural and sequence homology with the protease-inhibitory peptide SFTI-1 from sunflower. We refer to these as PawS-Derived Peptides (PDPs). The distribution of PDPs in several tribes and subtribes suggests that the origin of the unusual dual-fated PawS1-type gene was much more ancient than the Helianthus genus. Here we have used solution NMR spectroscopy to characterize the three-dimensional structures of a number of PDPs showing that in general they form well-defined, rigid structures with a diverse range of folds. Only close relatives of SFTI-1 are able to inhibit trypsin, with the functional significance of the remaining peptides yet to be understood.