title: Convergent evolution of defensin sequence, structure and function.
abstract: Defensins are a well-characterised group of small, disulphide-rich, cationic peptides that are produced by essentially all eukaryotes and are highly diverse in their sequences and structures. Most display broad range antimicrobial activity at low micromolar concentrations, whereas others have other diverse roles, including cell signalling (e.g. immune cell recruitment, self/non-self-recognition), ion channel perturbation, toxic functions, and enzyme inhibition. The defensins consist of two superfamilies, each derived from an independent evolutionary origin, which have subsequently undergone extensive divergent evolution in their sequence, structure and function. Referred to as the cis- and trans-defensin superfamilies, they are classified based on their secondary structure orientation, cysteine motifs and disulphide bond connectivities, tertiary structure similarities and precursor gene sequence. The utility of displaying loops on a stable, compact, disulphide-rich core has been exploited by evolution on multiple occasions. The defensin superfamilies represent a case where the ensuing convergent evolution of sequence, structure and function has been particularly extreme. Here, we discuss the extent, causes and significance of these convergent features, drawing examples from across the eukaryotes.
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, 3086, Australia.
authors.forename: Thomas M A
authors.identifier: 0000-0002-2298-7593
authors.initials: TM
authors.lastname: Shafee
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, 3086, Australia.
authors.forename: Fung T
authors.identifier: 0000-0002-3101-3782
authors.initials: FT
authors.lastname: Lay
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, 3086, Australia.
authors.forename: Thanh Kha
authors.initials: TK
authors.lastname: Phan
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, 3086, Australia. m.anderson@latrobe.edu.au.
authors.forename: Marilyn A
authors.identifier: 0000-0002-8257-5128
authors.initials: MA
authors.lastname: Anderson
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, 3086, Australia. m.hulett@latrobe.edu.au.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Hulett
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism; D023082:Defensins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D018628:Gene Dosage; D006801:Humans; D008958:Models, Molecular; D010802:Phylogeny; D011487:Protein Conformation; D016415:Sequence Alignment
chemical_list: D000890:Anti-Infective Agents; D023082:Defensins
keywords: Antimicrobial peptide; Disulphide-rich protein; Divergent evolution; Evolutionary constraint; Evolvability; Protein superfamily