title: Molecular basis for amyloid fibril formation and stability.
abstract: 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.
authors.affiliation: Structural Medicine, Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, Hills Road, Cambridge CB2 2XY, United Kingdom.
authors.forename: O Sumner
authors.initials: OS
authors.lastname: Makin
authors.forename: Edward
authors.initials: E
authors.lastname: Atkins
authors.forename: Pawel
authors.initials: P
authors.lastname: Sikorski
authors.forename: Jan
authors.initials: J
authors.lastname: Johansson
authors.forename: Louise C
authors.initials: LC
authors.lastname: Serpell
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D003460:Crystallization; D008854:Microscopy, Electron; D017433:Protein Structure, Secondary; D014961:X-Ray Diffraction
chemical_list: D000682:Amyloid