Plasticity of Amyloid Fibrils

• Published in: Biochemistry (Easton) Vol. 46; no. 1; pp. 1 - 10
• Main Authors: Wetzel, Ronald, Shivaprasad, Shankaramma, Williams, Angela D
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 09.01.2007
• Subjects: Amino Acid Sequence; Amyloid - chemistry; Amyloid - metabolism; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - metabolism; Animals; Humans; Models, Molecular; Molecular Sequence Data; Mutagenesis; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Polymers - chemistry; Polymers - metabolism; Protein Conformation
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi0620959

In experiments designed to characterize the basis of amyloid fibril stability through mutational analysis of the Aβ (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.