Work

Molecular basis for amyloid fibril formation and stability

Year: 2005

Type: article

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.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.0406847102

Authors: O. Sumner Makin, Edward Atkins, Pawel Sikorski, Jan Johansson, Louise C. Serpell

Institutions: Norwegian University of Science and Technology, University of Cambridge, University of Massachusetts Amherst, Swedish University of Agricultural Sciences

Language: English

Topic: Alzheimer's disease research and treatments

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

Open Access status: green

Funder: Wellcome Trust

OpenAlex ID: W2161163255

FWCI: 17.61

Cites: 39

Cited by: 663

Related to: 9