Identification of a novel 'aggregation-prone'/'amyloidogenic determinant' peptide in the sequence of the highly amyloidogenic human calcitonin

Abstract

Calcitonin is a 32-residue polypeptide hormone, which takes part in calcium metabolism in bones. It may form amyloid fibrils. Amyloid fibrils are related with serious diseases known as amyloidoses. The amyloid form of calcitonin takes part in medullary thyroid carcinoma. A novel hexapeptide ((6)TCMLGT(11)) of human calcitonin was predicted as a possible 'aggregation-prone' peptide, which may play a role in amyloid formation. We investigated experimentally the ability of an analog of this hexapeptide (cysteine replaced by alanine, TAMLGT) to form amyloid fibrils utilizing TEM, X-ray fiber diffraction, ATR FT-IR spectroscopy, and polarized light microscopy. This peptide self-assembles into amyloid-like fibrils and fibrillogenesis is mediated via nuclei of liquid crystalline nature, known as spherulites.