RESUMO
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.
Assuntos
Somatostatina/química , Amiloide/química , Cromatografia Líquida de Alta Pressão/métodos , Vermelho Congo/farmacologia , Cristalização , Técnica de Fratura por Congelamento , Hormônios/química , Hormônios/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Cristais Líquidos , Microscopia , Microscopia Eletrônica de Transmissão , Conformação Molecular , Nanopartículas/química , Hormônios Peptídicos/metabolismoRESUMO
We present some experimental and numerical results based on a simple model designed to give an estimate for the width of a shear zone. We conclude that the observed finite size of the shear zone can be associated with the propagation of the force lines inside the medium. The model, based on a simple argument on the force distribution and dilatancy, predicts a width of about ten grain diameters.
