Amino acid sequence determinants in self-assembly of insulin chiral amyloid superstructures: Role of C-terminus of B-chain in association of fibrils

Formation of chiral amyloid superstructures is a newly recognised phenomenon observed upon agitation-assisted fibrillation of bovine insulin. Here, by surveying several amyloidogenic precursors we examine whether formation of such entities is unique to bovine insulin. Our results indicate that only bovine, human, and porcine insulins are capable of chiral superstructural self-assembly. A tiny covalent perturbation consisting in reversal of Pro(B28)-Lys(B29) residues in a human insulin analog is sufficient to prevent this process. Our study suggests that insulin's dimer-forming interface - specifically the B-chain's C-terminal fragment - may acquire the new role of a molecular velcro upon lateral alignment of individual fibrils into superstructures. Structured summary of protein interactions: BI and BI bind by infrared spectroscopy (View interaction) HI and HI bind by atomic force microscopy (View interaction) HEWL and HEWL bind by circular dichroism (View interaction) BI and BI bind by circular dichroism (View interaction) alpha-LAC and alpha-LAC bind by circular dichroism (View interaction) BI and BI bind by atomic force microscopy (View interaction) alpha-LAC and alpha-LAC bind by atomic force microscopy (View interaction) HI and HI bind by circular dichroism (View interaction) PI and PI bind by circular dichroism (View interaction) PI and PI bind by atomic force microscopy (View interaction) HEWL and HEWL bind by atomic force microscopy (View interaction) (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.