title: Identification of a neuropeptide precursor protein that gives rise to a "cocktail" of peptides that bind Cu(II) and generate metal-linked dimers.
abstract: BACKGROUND
  Neuropeptides with an Amino Terminal Cu(II), Ni(II) Binding (ATCUN) motif (H2N-xxH) bind Cu(II)/Ni(II) ions. Here we report the novel discovery of a neuropeptide precursor that gives rise to a "cocktail" of peptides that bind Cu(II)/Ni(II) and form ternary complexes--the L-type SALMFamide precursor in the starfish Asterias rubens.
  
  
  METHODS
  Echinoderm transcriptome sequence data were analysed to identify transcripts encoding precursors of SALMFamide-type neuropeptides. The sequence of the L-type SALMFamide precursor in the starfish Asterias rubens was confirmed by cDNA sequencing and peptides derived from this precursor (e.g. AYHSALPF-NH2, GYHSGLPF-NH2 and LHSALPF-NH2) were synthesized. The ability of these peptides to bind metals was investigated using UV/Vis, NMR, circular dichroism and EPR spectroscopy.
  
  
  RESULTS
  AYHSALPF-NH2 and GYHSGLPF-NH2 bind Cu(II) and Ni(II) and generate metal-linked dimers to form ternary complexes with LHSALPF-NH2. Investigation of the evolutionary history of the histidine residue that confers these properties revealed that it can be traced to the common ancestor of echinoderms, which is estimated to have lived ~500 million years ago. However, L-type precursors comprising multiple SALMFamides with the histidine residue forming an ATCUN motif appears to be a feature that has evolved uniquely in starfish (Asteroidea).
  
  
  CONCLUSIONS
  The discovery of a SALMFamide-type neuropeptide precursor protein that gives rise to a "cocktail" of peptides that bind metal ions and generate metal-linked dimers provides a new insight on ATCUN motif-containing neuropeptides. This property of L-type SALMFamides in the Asteroidea may be associated with a role in regulation of the unusual extra-oral feeding behaviour of starfish.
authors.affiliation: School of Science and Health, Western Sydney University, Locked bag 1797, Penrith, 2751, New South Wales, Australia. Electronic address: c.jones@uws.edu.au.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Jones
authors.affiliation: School of Biological & Chemical Sciences, Queen Mary University of London, Mile End Road, London, E1 4NS, UK.
authors.forename: Meet
authors.initials: M
authors.lastname: Zandawala
authors.affiliation: School of Biological & Chemical Sciences, Queen Mary University of London, Mile End Road, London, E1 4NS, UK.
authors.forename: Dean C
authors.initials: DC
authors.lastname: Semmens
authors.affiliation: School of Biological & Chemical Sciences, Queen Mary University of London, Mile End Road, London, E1 4NS, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Anderson
authors.affiliation: Centre for Advanced Imaging, The University of Queensland, Brisbane, Queensland, 4072, Australia.
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Hanson
authors.affiliation: Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC, 28223, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Janies
authors.affiliation: School of Biological & Chemical Sciences, Queen Mary University of London, Mile End Road, London, E1 4NS, UK. Electronic address: m.r.elphick@qmul.ac.uk.
authors.forename: Maurice R
authors.initials: MR
authors.lastname: Elphick
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry*; D055503:Protein Multimerization; D011498:Protein Precursors / Q000737:chemistry*; D013215:Starfish
chemical_list: D009479:Neuropeptides; D011498:Protein Precursors; D003300:Copper
keywords: ATCUN; Copper; Echinoderm; Neuropeptide; SALMFamide; Starfish