Molecular basis for amyloid fibril formation and stability.
The molecular structure of the amyloid fibril has remained elusive because of the difficulty of growing well diffracting crystals. By using a sequence-designed polypeptide, we have produced crystals of an amyloid fiber. These crystals diffract to high resolution (1 A) by electron and x-ray diffraction, enabling us to determine a detailed structure for amyloid. The structure reveals that the polypeptides form fibrous crystals composed of antiparallel beta-sheets in a cross-beta arrangement, characteristic of all amyloid fibers, and allows us to determine the side-chain packing within an amyloid fiber. The antiparallel beta-sheets are zipped together by means of pi-bonding between adjacent phenylalanine rings and salt-bridges between charge pairs (glutamic acid-lysine), thus controlling and stabilizing the structure. These interactions are likely to be important in the formation and stability of other amyloid fibrils.
Makin
O Sumner
OS
Structural Medicine, Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, Hills Road, Cambridge CB2 2XY, United Kingdom.
Atkins
Edward
E
Sikorski
Pawel
P
Johansson
Jan
J
Serpell
Louise C
LC
D000682:Amyloid / Q000737:chemistry*; D003460:Crystallization; D008854:Microscopy, Electron; D017433:Protein Structure, Secondary; D014961:X-Ray Diffraction
D000682:Amyloid