[Show abstract][Hide abstract] ABSTRACT: The native hierarchical self-assembly process of natural somatostatin-14, a highly aromatic and charged peptide hormone involved in various inhibitory functions, was investigated mainly using vibrational spectroscopy (ATR-FTIR and Raman scattering) combined with electron microscopy. Generic kinetic features of amyloid fibrillogenesis were confirmed for the somatostatin-14 case, together with new insights into key interactions involved in the further hierarchical assembly of the somatostatin-14 nanofibrils into i) laterally associated nanofibers and ii) spherulite-like amyloid droplets resulting from the compaction of the nanofibers. In particular, the key role of aromatic side-chains in both fibrillogenesis and the association of the nanofibrils into higher order structures could be followed. It is proposed that the compaction propensity of the somatostatin-14 nanofibrils is relevant to the current hypothesis of the biological function of hormone self-assembly processes: hormone storage inside secretory granules.
[Show abstract][Hide abstract] 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.
Journal of Structural Biology 12/2007; 160(2):211-23. · 3.36 Impact Factor