van Grondelle Wilmar, Iglesias Carmen López, Coll Elisenda, Artzner Franck, Paternostre Maïté, Lacombe Frédéric, Cardus Merce, Martinez Gema, Montes Martin, Cherif-Cheikh Roland, Valéry Céline
Ipsen Pharma, Carrer Laureà Miró 395, Sant Feliu de Llobregat, 08980 Barcelona, Spain.
J Struct Biol. 2007 Nov;160(2):211-23. doi: 10.1016/j.jsb.2007.08.006. Epub 2007 Aug 23.
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.
天然生长抑素-14是一种小型环状神经肽激素，对内分泌分泌具有广泛的抑制作用。我们在此表明，天然生长抑素-14在水中和150 mM氯化钠中会自发自组装成液晶纳米纤维，这些纳米纤维具有淀粉样纤维的特征性结构特征。这些非共价的高度稳定结构基于生长抑素的天然主链构象，且在非变性条件下形成。我们的结果支持了这样一种假说，即在适当条件下，自组装成淀粉样纤维是多肽链的一种普遍特性。鉴于近期在肽/蛋白质激素生物储存机制以及分泌颗粒分选模式方面取得的进展，我们提出生长抑素-14的纤维化可能与这种神经肽激素的调节分泌途径相关。这样的假说与非疾病相关但具有功能的淀粉样蛋白存在这一新兴概念相一致。
