title: Cross-seeding of fibrils from two types of insulin induces new amyloid strains.
abstract: The irreversibility and autocatalytic character of amyloidogenesis and the polymorphism of amyloid fibrils underlie the phenomenon of self-propagating strains, wherein the mother seed, rather than the seeding environment, determines the properties of daughter fibrils. Here we study the formation of amyloid fibrils from bovine insulin and the recombinant Lys(B31)-Arg(B32) human insulin analog. The two polypeptides are similar enough to cross-seed but, upon spontaneous aggregation, form amyloid fibrils with distinct spectral features in the infrared amide I' band region. When bovine insulin is cross-seeded with the analog amyloid (and vice versa), the shape, absorption maximum, and even fine fingerprint features of the amide I' band are passed from the mother to daughter fibrils with a high degree of fidelity. Although the differences in primary structure between bovine insulin and the Lys(B31)-Arg(B32) analog of human insulin lie outside of the polypeptide's critical amyloidogenic regions, they affect the secondary structure of fibrils, possibly the formation of intermolecular salt bridges, and the susceptibility to dissection and denaturation with dimethyl sulfoxide (DMSO). All these phenotypic features of mother fibrils are imprinted in daughter amyloid upon cross-seeding. Analysis of noncooperative DMSO-induced denaturation of daughter fibrils suggests that the self-propagating polymorphism underlying the emergence of new amyloid strains is encoded on the level of secondary structure. Our findings have been discussed in the context of polymorphism of fibrils, amyloid strains, and possible implications for mechanisms of amyloidogenesis.
authors.affiliation: Institute of Biotechnology and Antibiotics, Staroscinska 5, 02-516 Warsaw, Poland.
authors.forename: Weronika
authors.initials: W
authors.lastname: Surmacz-Chwedoruk
authors.forename: Hanna
authors.initials: H
authors.lastname: Nieznańska
authors.forename: Sławomir
authors.initials: S
authors.lastname: Wójcik
authors.forename: Wojciech
authors.initials: W
authors.lastname: Dzwolak
mesh_terms: D000577:Amides / Q000737:chemistry; D019943:Amino Acid Substitution; D000682:Amyloid / Q000737:chemistry*; D000818:Animals; D002417:Cattle; D003903:Deuterium; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives* / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D011489:Protein Denaturation; D011994:Recombinant Proteins / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000577:Amides; D000682:Amyloid; D007328:Insulin; D011994:Recombinant Proteins; C577648:insulin, lysyl(B31)-arginyl(B32)-; D003903:Deuterium; D004121:Dimethyl Sulfoxide