The Structure of Amyloid

The local or systemic deposition of insoluble amyloid fibrils is characteristic of the pathogenesis of the heterogeneous group of diseases known as the amyloidoses. Normally soluble, innocuous proteins undergo a change in conformation and self assemble into insoluble, potentially toxic, amyloid fibrils. Electron microscopy shows amyloid fibrils to be straight, unbranching structures, 70 to 120 Å in diameter and of indeterminate length. The potential for amyloidogenesis may be a near universal property of protein. Knowledge of the structure of these fibrils is a crucial element in the development of an understanding of their stability and assembly. With this information, the rational design of drugs to prevent amyloidogenesis and promote disassembly might be enabled. Furthermore, it may grant some insight into the generality of protein folding. Single crystal X-ray crystallography and solution NMR are not possible due to the fibrillar inability to crystallise and to intrinsic insolubility. X-ray and recently electron fibre diffraction have proved to be of great value in the elucidation of the structure of amyloid. This review discusses the advances made and how fibre diffraction is used in conjunction with other structural technique.