Quaternary structure of a mature amyloid fibril from Alzheimer's Abeta(1-40) peptide.

Amyloid fibrils are fibrous polypeptide aggregates that can be formed in vitro and under pathologic conditions, such as in type II diabetes, Alzheimer's and Creutzfeldt-Jakob diseases. Using a range of biophysical techniques including electron microscopy we have analysed the quaternary structure of a mature amyloid fibril formed from the Abeta(1-40) peptide from Alzheimer's disease. We find that the analysed fibril is discernibly polar and represents a left-handed helix consisting of two or three protofilaments. These are organised in a manner so that the cross-section is, under the present resolution conditions (2.6 nm), S-shaped. In the cross-section, each protofilament can accommodate two beta-strands, suggesting that each protofilament contains two cross-beta-sheets. These data shed new light on the way in which Abeta(1-40) and the protofilaments formed from this peptide are organised within the mature fibril.