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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.

SUBMITTER: Makin OS

PROVIDER: S-EPMC544296 | biostudies-literature | 2005 Jan

REPOSITORIES: biostudies-literature

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Molecular basis for amyloid fibril formation and stability.

Makin O Sumner OS Atkins Edward E Sikorski Pawel P Johansson Jan J Serpell Louise C LC

Proceedings of the National Academy of Sciences of the United States of America 20050103 2

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, chara ...[more]

PMID: 15630094

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