Amyloid Architecture: Complementary Assembly of Heterogeneous Combinations of Three or Four Peptides into Amyloid Fibrils

Abstract

The amyloid fibril is a misfolded and undesirable state for proteins that has been proposed to be a causative agent for a variety of fatal diseases known as amyloid diseases, such as Alzheimer's and prion diseases. However, the fibril has a highly ordered tertiary structure in which numerous β-strand polypeptide chains align in a regular pattern. Thus, this kind of fibril has the potential to be engineered into proteinaceous materials. Amyloid fibrils of misfolded proteins primarily comprise a single polypeptide species, that is, the self-assembly is homogeneous. We here found that three or four designed peptides can assemble heterogeneously and cooperatively into amyloid fibrils, a process accompanied by a drastic secondary structural transition from α helix to β sheet. Heterogeneous assembly into fibrils is accomplished by complementary electrostatic interactions between three or four peptide species, each of which is not able to self-assemble homogeneously. These findings will lead to a novel way to study the molecular details of amyloid formation and also to design β-sheet peptidyl materials.