Solution conditions can promote formation of either amyloid protofilamentsor mature fibrils from the HypF N-terminal domain

The HypF N-terminal domain has been found to convert readily from its nativ e globular conformation into protein aggregates with the characteristics of amyloid fibrils associated with a variety of human diseases. This conversi on was achieved by incubation at acidic pH or in the presence of moderate c oncentrations of trifluoroethanol. Electron microscopy showed that the fibr ils grown in the presence of trifluoro ethanol were predominantly 3-5 nm an d 7-9 nm in width, whereas fibrils of 7-9 nm and 12-20 nm in width prevaile d in samples incubated at acidic pH. These results indicate that the assemb ly of protofilaments or narrow fibrils into mature amyloid fibrils is guide d by interactions between hydrophobic residues that may remain exposed on t he surface of individual protofilaments. Therefore, formation and isolation of individual protofilaments appears facilitated under conditions that fav or the destabilization of hydrophobic interactions, such as in the presence of trifluoroethanol.