UCLA

We report here that a monomeric de novo designed α-helix-turn-α-helix peptide, αtα, when incubated at 37 °C in an aqueous buffer at neutral pH, forms nonbranching, protease resistant fibrils that are 6–10 nm in diameter. These fibrils are rich in β-sheet and bind the amyloidophilic dye Congo red. αtα fibrils thus display the morphologic, structural, and tinctorial properties of authentic amyloid fibrils. Surprisingly, unlike fibrils formed by peptides such as the amyloid β-protein or the islet amyloid polypeptide, αtα fibrils were not toxic to cultured rat primary cortical neurons or PC12 cells. These results suggest that the potential to form fibrils under physiologic conditions is not limited to those proteins associated with amyloidoses and that fibril formation alone is not predictive of cytotoxic activity.