title: Spontaneous fibrillation of the native neuropeptide hormone Somatostatin-14.
abstract: Natural Somatostatin-14 is a small cyclic neuropeptide hormone with broad inhibitory effects on endocrine secretions. Here we show that natural Somatostatin-14 spontaneously self-assembles in water and in 150 mM NaCl into liquid crystalline nanofibrils, which follow characteristic structural features of amyloid fibrils. These non-covalent highly stable structures are based on the Somatostatin native backbone conformation and are formed under non-denaturing conditions. Our results support the hypothesis that self-assembly into amyloid fibrils is a generic property of the polypeptide chain under appropriate conditions. Given recent advances on the mechanisms of biological storage and sorting modes of peptide/protein hormones into secretory granules, we propose that Somatostatin-14 fibrillation could be relevant to the regulated secretion pathway of this neuropeptide hormone. Such a hypothesis is consistent with the emerging concept of the existence of non-disease related but functional amyloids.
authors.affiliation: Ipsen Pharma, Carrer Laureà Miró 395, Sant Feliu de Llobregat, 08980 Barcelona, Spain.
authors.forename: Wilmar
authors.initials: W
authors.lastname: van Grondelle
authors.forename: Carmen López
authors.initials: CL
authors.lastname: Iglesias
authors.forename: Elisenda
authors.initials: E
authors.lastname: Coll
authors.forename: Franck
authors.initials: F
authors.lastname: Artzner
authors.forename: Maïté
authors.initials: M
authors.lastname: Paternostre
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lacombe
authors.forename: Merce
authors.initials: M
authors.lastname: Cardus
authors.forename: Gema
authors.initials: G
authors.lastname: Martinez
authors.forename: Martin
authors.initials: M
authors.lastname: Montes
authors.forename: Roland
authors.initials: R
authors.lastname: Cherif-Cheikh
authors.forename: Céline
authors.initials: C
authors.lastname: Valéry
mesh_terms: D000682:Amyloid / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003224:Congo Red / Q000494:pharmacology; D003460:Crystallization; D005614:Freeze Fracturing; D006728:Hormones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D050866:Liquid Crystals; D008853:Microscopy; D046529:Microscopy, Electron, Transmission; D008968:Molecular Conformation; D053758:Nanoparticles / Q000737:chemistry; D036361:Peptide Hormones / Q000378:metabolism; D013004:Somatostatin / Q000737:chemistry*
chemical_list: D000682:Amyloid; D006728:Hormones; D036361:Peptide Hormones; D003224:Congo Red; D013004:Somatostatin