Sawaya, M. R. et al. Atomic structures of amyloid cross- spines reveal varied steric zippers. Nature 447, 453-457

Howard Hughes Medical Institute, UCLA-DOE Institute of Genomics and Proteomics, Los Angeles, California 90095-1570, USA.
Nature (Impact Factor: 41.46). 06/2007; 447(7143):453-7. DOI: 10.1038/nature05695
Source: PubMed


Amyloid fibrils formed from different proteins, each associated with a particular disease, contain a common cross-beta spine. The atomic architecture of a spine, from the fibril-forming segment GNNQQNY of the yeast prion protein Sup35, was recently revealed by X-ray microcrystallography. It is a pair of beta-sheets, with the facing side chains of the two sheets interdigitated in a dry 'steric zipper'. Here we report some 30 other segments from fibril-forming proteins that form amyloid-like fibrils, microcrystals, or usually both. These include segments from the Alzheimer's amyloid-beta and tau proteins, the PrP prion protein, insulin, islet amyloid polypeptide (IAPP), lysozyme, myoglobin, alpha-synuclein and beta(2)-microglobulin, suggesting that common structural features are shared by amyloid diseases at the molecular level. Structures of 13 of these microcrystals all reveal steric zippers, but with variations that expand the range of atomic architectures for amyloid-like fibrils and offer an atomic-level hypothesis for the basis of prion strains.

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    • "We focused on the two partially overlapping segments 252-LTIITLE-258 and 253- TIITLE-258, and chemically synthesized them. Both formed amyloid-like fibrils and microcrystals that enabled their structure determination at atomic resolution (Sawaya et al., 2007; Figure S1 and Table S1). The segments aggregated as tight, dry steric zippers , with LTIITLE forming a class 2, face-to-back amyloid spine while TIITLE formed a class 1, face-to-face interface. "
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