title: Toxin structures as evolutionary tools: Using conserved 3D folds to study the evolution of rapidly evolving peptides.
abstract: Three-dimensional (3D) structures have been used to explore the evolution of proteins for decades, yet they have rarely been utilized to study the molecular evolution of peptides. Here, we highlight areas in which 3D structures can be particularly useful for studying the molecular evolution of peptide toxins. Although we focus our discussion on animal toxins, including one of the most widespread disulfide-rich peptide folds known, the inhibitor cystine knot, our conclusions should be widely applicable to studies of the evolution of disulfide-constrained peptides. We show that conserved 3D folds can be used to identify evolutionary links and test hypotheses regarding the evolutionary origin of peptides with extremely low sequence identity; construct accurate multiple sequence alignments; and better understand the evolutionary forces that drive the molecular evolution of peptides. Also watch the video abstract.
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland, Australia.
authors.forename: Eivind A B
authors.initials: EA
authors.lastname: Undheim
authors.affiliation: Centre for Advanced Imaging, University of Queensland, St Lucia, Queensland, Australia.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mobli
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland, Australia.
authors.forename: Glenn F
authors.initials: GF
authors.lastname: King
mesh_terms: D000818:Animals; D056890:Eukaryota / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014118:Toxins, Biological / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014780:Viruses / Q000235:genetics / Q000378:metabolism
chemical_list: D010455:Peptides; D014118:Toxins, Biological
keywords: inhibitor cystine knot; knottin; protein evolution; structural adaptation; toxin