title: pH-Driven Polymorphism of Insulin Amyloid-Like Fibrils.
abstract: Prions are infective proteins, which can self-assemble into different strain conformations, leading to different disease phenotypes. An increasing number of studies suggest that prion-like self-propagation may be a common feature of amyloid-like structures. Thus it is important to unravel every possible factor leading to the formation of different amyloid strains. Here we report on the formation of two types of insulin amyloid-like fibrils with distinct infrared spectroscopic features grown under slightly different pH conditions. Similar to prion strains, both insulin fibril types are able to self-propagate their conformational template under conditions, favoring spontaneous formation of different type fibrils. The low-pH-induced insulin amyloid strain is structurally very similar to previously reported strains formed either in the presence of 20% ethanol, or by modification of the amino acid sequence of insulin. A deeper analysis of literature data in the context of our current findings suggests a shift of the monomer-dimer equilibrium of insulin as a possible factor controlling the formation of different strains.
authors: Department of Biothermodynamics and Drug Design, Vilnius University Institute of Biotechnology, Vilnius, Lithuania.
authors: Tomas
authors: T
authors: Sneideris
authors: Department of Biothermodynamics and Drug Design, Vilnius University Institute of Biotechnology, Vilnius, Lithuania.
authors: Domantas
authors: D
authors: Darguzis
authors: Department of Biothermodynamics and Drug Design, Vilnius University Institute of Biotechnology, Vilnius, Lithuania.
authors: Akvile
authors: A
authors: Botyriute
authors: Department of Biothermodynamics and Drug Design, Vilnius University Institute of Biotechnology, Vilnius, Lithuania.
authors: Martynas
authors: M
authors: Grigaliunas
authors: Physical Chemistry I-Biophysical Chemistry, Faculty of Chemistry and Chemical Biology, TU Dortmund University, Dortmund, Germany.
authors: Roland
authors: R
authors: Winter
authors: Department of Biothermodynamics and Drug Design, Vilnius University Institute of Biotechnology, Vilnius, Lithuania.
authors: Vytautas
authors: V
authors: Smirnovas
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure; D000431:Ethanol / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000737:chemistry*; D066329:Protein Aggregates
chemical_list: D000682:Amyloid; D007328:Insulin; D066329:Protein Aggregates; D000431:Ethanol