Spontaneous fibrillation of the native neuropeptide hormone Somatostatin-14.
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.
van Grondelle
Wilmar
W
Ipsen Pharma, Carrer Laureà Miró 395, Sant Feliu de Llobregat, 08980 Barcelona, Spain.
Iglesias
Carmen López
CL
Coll
Elisenda
E
Artzner
Franck
F
Paternostre
Maïté
M
Lacombe
Frédéric
F
Cardus
Merce
M
Martinez
Gema
G
Montes
Martin
M
Cherif-Cheikh
Roland
R
Valéry
Céline
C
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*
D000682:Amyloid; D006728:Hormones; D036361:Peptide Hormones; D003224:Congo Red; D013004:Somatostatin