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.
Subject(s)
Somatostatin/chemistry , Amyloid/chemistry , Chromatography, High Pressure Liquid/methods , Congo Red/pharmacology , Crystallization , Freeze Fracturing , Hormones/chemistry , Hormones/metabolism , Humans , Hydrogen-Ion Concentration , Liquid Crystals , Microscopy , Microscopy, Electron, Transmission , Molecular Conformation , Nanoparticles/chemistry , Peptide Hormones/metabolismABSTRACT
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.
