34] X-Ray fiber diffraction of amyloid fibrils

Abstract

Amyloid is an ordered structure generated by the polymerization of amyloidogenic proteins. It is a high molecular weight, insoluble material and therefore the atomic structure cannot be investigated by conventional X-ray crystallography or nuclear magnetic resonance (NMR). However, information about its overall fibrillar structure can be obtained by X-ray fiber diffraction, particularly if high-resolution data can be collected. The earliest reported use of this technique, investigating serum amyloid A and light chain amyloid, reoported meridional reflections at 4.68 Å and equatorial reflections at 9.8 Å. These diffraction patterns are consistent with fibrils composed of polypeptide chains extended in the so-called cross-β conformation, a structure that had earlier been identified as a possible conformation for polypeptide chains on the grounds of model building by Pauling and Corey and which was described for insect silk (Crysopa) by Geddes and co-workers. The meridional reflection indicates a regular structural repeat of 4.68 Å along the fibril axis, and the equatorial reflection indicates a structural spacing of 9.8 Å perpendicular to the fibril axis.