A de novo designed helix-turn-helix peptide forms nontoxic amyloid fibrils

We report here that a monomeric de novo designed alpha -helix-turn-alpha -helix peptide, alphat alpha, when incubated at 37 degreesC in an aqueous buffer at neutral pH, forms nonbranching, protease resistant fibrils that are 6-10 nn in diameter. These fibrils are rich in beta -sheet and bind the amyloidophilic dye Congo red. alphat alpha fibrils thus display the morphologic, structural, and tinctorial properties of authentic amyloid fibrils. Surprisingly, unlike fibrils formed by peptides such as the amyloid beta -protein or the islet amyloid polypeptide, alphat alpha 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.