title: Amyloid fibril formation by pentapeptide and tetrapeptide fragments of human calcitonin.
abstract: The process of amyloid fibril formation by the human calcitonin hormone is associated with medullary thyroid carcinoma. Based on the effect of pH on the fibrillization of human calcitonin, the analysis of conformationally constrained analogues of the hormone, and our suggestion regarding the role of aromatic residues in the process of amyloid fibril formation, we studied the ability of a short aromatic charged peptide fragment of calcitonin (NH(2)-DFNKF-COOH) to form amyloid fibrils. Here, using structural and biophysical analysis, we clearly demonstrate the ability of this short peptide to form well ordered amyloid fibrils. A shorter truncated tetrapeptide, NH(2)-DFNK-COOH, also formed fibrils albeit less ordered than those formed by the pentapeptide. We could not detect amyloid fibril formation by the NH(2)-FNKF-COOH tetrapeptide, the NH(2)-DFN-COOH tripeptide, or the NH(2)-DANKA-COOH phenylalanine to the alanine analogue of the pentapeptide. The formation of amyloid fibrils by rather hydrophilic peptides is quite striking, because it was speculated that hydrophobic interactions might play a key role in amyloid formation. This is the first reported case of fibril formation by a peptide as short as a tetrapeptide and one of very few cases of amyloid formation by pentapeptides. Because the aromatic nature seems to be the only common property of the various very short amyloid-forming peptides, it further supports our hypothesis on the role of aromatic interactions in the process of amyloid fibril formation.
authors.affiliation: Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel.
authors.forename: Meital
authors.initials: M
authors.lastname: Reches
authors.forename: Yair
authors.initials: Y
authors.lastname: Porat
authors.forename: Ehud
authors.initials: E
authors.lastname: Gazit
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000096:biosynthesis*; D002116:Calcitonin / Q000737:chemistry*; D003224:Congo Red; D006801:Humans; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000502:physiology*; D010446:Peptide Fragments / Q000737:chemistry / Q000502:physiology*; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000682:Amyloid; D009842:Oligopeptides; D010446:Peptide Fragments; D003224:Congo Red; D002116:Calcitonin