Atomic structures of amyloid cross-β spines reveal varied steric zippers

TY - JOUR

T1 - Atomic structures of amyloid cross-β spines reveal varied steric zippers

AU - Sawaya, Michael R.

AU - Sambashivan, Shilpa

AU - Nelson, Rebecca

AU - Ivanova, Magdalena I.

AU - Sievers, Stuart A.

AU - Apostol, Marcin I.

AU - Thompson, Michael J.

AU - Balbirnie, Melinda

AU - Wiltzius, Jed J.W.

AU - McFarlane, Heather T.

AU - Madsen, Anders

AU - Riekel, Christian

AU - Eisenberg, David

PY - 2007/5/24

Y1 - 2007/5/24

N2 - Amyloid fibrils formed from different proteins, each associated with a particular disease, contain a common cross-β 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 β-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-β and tau proteins, the PrP prion protein, insulin, islet amyloid polypeptide (IAPP), lysozyme, myoglobin, α-synuclein and β2-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.

AB - Amyloid fibrils formed from different proteins, each associated with a particular disease, contain a common cross-β 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 β-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-β and tau proteins, the PrP prion protein, insulin, islet amyloid polypeptide (IAPP), lysozyme, myoglobin, α-synuclein and β2-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.

UR - http://www.scopus.com/inward/record.url?scp=34249290108&partnerID=8YFLogxK

U2 - 10.1038/nature05695

DO - 10.1038/nature05695

M3 - Journal article

C2 - 17468747

AN - SCOPUS:34249290108

SN - 0028-0836

VL - 447

SP - 453

EP - 457

JO - Nature

JF - Nature

IS - 7143

ER -