A molecular model of the amyloid fibril.
We have investigated the ultrastructure of the homozygous amyloid fibrils from the vitreous humour of patients with Met30 familial amyloidotic polyneuropathy (FAP) by high-resolution electron microscopy and X-ray diffraction using synchrotron radiation. Image reconstruction of thin sections of Met30 FAP fibrils shows that they are composed of four parallel protofilaments, 50-60 A in diameter, arranged in a square around a hollow centre. The X-ray diffraction patterns are consistent with the presence in the protofilaments of a repeating unit of 24 beta-strands forming a continuous beta-sheet extended along the fibre axis, with the beta-strands perpendicular to the axis. We have characterized this repeat unit as one turn of a beta-sheet helix. This newly-described helix reconciles the classical cross-beta structure of amyloid with the twisted beta-sheet that is known to be the most stable form of the structure. All four beta-sheets composing the protofilament twist around a single helical axis which is coincident with the axis of the protofilament. Other amyloid diffraction patterns are similar to that of FAP, suggesting that the beta-sheet helix may be the generic core structure of amyloid.
Laboratory of Molecular Biophysics, University of Oxford, UK.
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Blake
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Serpell
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M
Sunde
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O
Sandgren
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Lundgren
D000682:Amyloid / Q000032:analysis / Q000648:ultrastructure*; D000686:Amyloidosis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008854:Microscopy, Electron; D008958:Models, Molecular; D014961:X-Ray Diffraction
D000682:Amyloid