Core structure of amyloid fibrils formed by residues 106-126 of the human prion protein.

Peptides comprising residues 106-126 of the human prion protein (PrP) exhibit many features of the full-length protein. PrP(106-126) induces apoptosis in neurons, forms fibrillar aggregates, and can mediate the conversion of native cellular PrP (PrP(C)) to the scrapie form (PrP(Sc)). Despite a wide range of biochemical and biophysical studies on this peptide, including investigation of its propensity for aggregation, interactions with cell membranes, and PrP-like toxicity, the structure of amyloid fibrils formed by PrP(106-126) remains poorly defined. In this study we use solid-state nuclear magnetic resonance to define the secondary and quaternary structure of PrP(106-126) fibrils. Our results reveal that PrP(106-126) forms in-register parallel beta sheets, stacked in an antiparallel fashion within the mature fibril. The close intermolecular contacts observed in the fibril core provide a rational for the sequence-dependent behavior of PrP(106-126), and provide a basis for further investigation of its biological properties.