title: Plasticity of amyloid fibrils.
abstract: In experiments designed to characterize the basis of amyloid fibril stability through mutational analysis of the Abeta (1-40) molecule, fibrils exhibit consistent, significant structural malleability. In these results, and in other properties, amyloid fibrils appear to more resemble plastic materials generated from synthetic polymers than globular proteins. Thus, like synthetic polymers and plastics, amyloid fibrils exhibit both polymorphism, the ability of one polypeptide to form aggregates of different morphologies, and isomorphism, the ability of different polypeptides to grow into a fibrillar amyloid morphology. This view links amyloid with the prehistorical and 20th century use of proteins as starting materials to make films, fibers, and plastics, and with the classic protein fiber stretching experiments of the Astbury group. Viewing amyloids from the point of view of the polymer chemist may shed new light on a number of issues, such as the role of protofibrils in the mechanism of amyloid formation, the biological potency of fibrils, and the prospects for discovering inhibitors of amyloid fibril formation.
authors.affiliation: Graduate School of Medicine, University of Tennessee, Knoxville Tennessee 37920, USA. rwetzel@pitt.edu
authors.forename: Ronald
authors.initials: R
authors.lastname: Wetzel
authors.forename: Shankaramma
authors.initials: S
authors.lastname: Shivaprasad
authors.forename: Angela D
authors.initials: AD
authors.lastname: Williams
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011108:Polymers; C078592:amyloid beta-protein (1-40)