Examining the structure of the mature amyloid fibril.
The pathogenesis of the group of diseases known collectively as the amyloidoses is characterized by the deposition of insoluble amyloid fibrils. These are straight, unbranching structures about 70-120 A (1 A=0.1 nm) in diameter and of indeterminate length formed by the self-assembly of a diverse group of normally soluble proteins. Knowledge of the structure of these fibrils is necessary for the understanding of their abnormal assembly and deposition, possibly leading to the rational design of therapeutic agents for their prevention or disaggregation. Structural elucidation is impeded by fibril insolubility and inability to crystallize, thus preventing the use of X-ray crystallography and solution NMR. CD, Fourier-transform infrared spectroscopy and light scattering have been used in the study of the mechanism of fibril formation. This review concentrates on the structural information about the final, mature fibril and in particular the complementary techniques of cryo-electron microscopy, solid-state NMR and X-ray fibre diffraction.
Structural Medicine Unit, Cambridge Institute for Medical Research, Hills Road, Cambridge CB2 2XY, UK.
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Makin
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Serpell
D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000648:ultrastructure; D000686:Amyloidosis / Q000503:physiopathology; D020285:Cryoelectron Microscopy; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008854:Microscopy, Electron; D019636:Neurodegenerative Diseases / Q000473:pathology; D014961:X-Ray Diffraction
D016229:Amyloid beta-Peptides