title: Structural analysis of the starfish SALMFamide neuropeptides S1 and S2: the N-terminal region of S2 facilitates self-association.
abstract: The neuropeptides S1 (GFNSALMFamide) and S2 (SGPYSFNSGLTFamide), which share sequence similarity, were discovered in the starfish Asterias rubens and are prototypical members of the SALMFamide family of neuropeptides in echinoderms. SALMFamide neuropeptides act as muscle relaxants and both S1 and S2 cause relaxation of cardiac stomach and tube foot preparations in vitro but S2 is an order of magnitude more potent than S1. Here we investigated a structural basis for this difference in potency using spectroscopic techniques. Circular dichroism spectroscopy showed that S1 does not have a defined structure in aqueous solution and this was supported by 2D nuclear magnetic resonance experiments. In contrast, we found that S2 has a well-defined conformation in aqueous solution. However, the conformation of S2 was concentration dependent, with increasing concentration inducing a transition from an unstructured to a structured conformation. Interestingly, this property of S2 was not observed in an N-terminally truncated analogue of S2 (short S2 or SS2; SFNSGLTFamide). Collectively, the data obtained indicate that the N-terminal region of S2 facilitates peptide self-association at high concentrations, which may have relevance to the biosynthesis and/or bioactivity of S2 in vivo.
authors.affiliation: School of Biological & Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, UK.
authors.forename: Claire B
authors.initials: CB
authors.lastname: Otara
authors.affiliation: School of Biological & Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, UK; School of Science and Health, The University of Western Sydney, Locked bag 1797, Penrith 2751, Sydney, Australia.
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: Nadine D
authors.initials: ND
authors.lastname: Younan
authors.affiliation: School of Biological & Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, UK. Electronic address: j.viles@qmul.ac.uk.
authors.forename: John H
authors.initials: JH
authors.lastname: Viles
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: D000818:Animals; D047271:Asterias / Q000378:metabolism*; D002942:Circular Dichroism; D009479:Neuropeptides / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization
chemical_list: D009479:Neuropeptides; C069624:SALMFamide 1; C069625:SALMFamide 2
keywords: Circular dichroism; Muscle relaxant; NMR; Neuropeptide; SALMFamide; Self-association