Acetone-induced structural variant of insulin amyloid fibrils.

Self-propagating polymorphism of amyloid fibrils is a distinct manifestation of non-equilibrium conditions under which protein aggregation typically occurs. Structural variants of fibrils can often be accessed through physicochemical perturbations of the de novo aggregation process. On the other hand, tiny changes in the amino acid sequence of the parent protein may also result in structurally distinguishable amyloid fibrils.

Self-Assembly of Insulin-Derived Chimeric Peptides into Two-Component Amyloid Fibrils: The Role of Coulombic Interactions.

Canonical amyloid fibrils are composed of covalently identical polypeptide chains. Here, we employ kinetic assays, atomic force microscopy, infrared spectroscopy, circular dichroism, and molecular dynamics simulations to study fibrillization patterns of two chimeric peptides, ACCE and ACCK, in which a potent amyloidogenic stretch derived from the N-terminal segment of the insulin A-chain (ACC) is coupled to octaglutamate or octalysine segments, respectively. While large electric charges prevent aggregation of either peptide at neutral pH, stoichiometric mixing of ACCE and ACCK triggers rapid self-assembly of two-component fibrils driven by favorable Coulombic interactions.

Reduction of a disulfide-constrained oligo-glutamate peptide triggers self-assembly of β-type amyloid fibrils with the chiroptical properties determined by supramolecular chirality.

Disulfide bonds prevent aggregation of globular proteins by stabilizing the native state. However, a disulfide bond within a disordered state may accelerate amyloidogenic nucleation by navigating fluctuating polypeptide chains towards an orderly assembly of β-sheets. Here, the self-assembly behavior of Glu-Cys-(Glu)-Cys-Glu peptide (EC), in which an intrachain disulfide bond is engineered into an amyloidogenic homopolypeptide motif, is investigated.

Reversible Freeze-Induced β-Sheet-to-Disorder Transition in Aggregated Homopolypeptide System.

Conformational transitions involving aggregated proteins or peptides are of paramount biomedical and biotechnological importance. Here, we report an unusual freeze-induced structural reorganization within a β-sheet-rich ionic coaggregate of poly(l-lysine), PLL, and poly(l-glutamic acid), PLGA. Freezing aqueous suspensions of the PLL-PLGA β-aggregate in the presence of low concentrations of salt (NaBr) induces an instantaneous β-sheet-to-disorder transition, as probed by infrared spectroscopy in the amide I' band region.