title: Atomic structures of amyloid cross-beta spines reveal varied steric zippers.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, UCLA-DOE Institute of Genomics and Proteomics, Los Angeles, California 90095-1570, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Sawaya
authors.forename: Shilpa
authors.initials: S
authors.lastname: Sambashivan
authors.forename: Rebecca
authors.initials: R
authors.lastname: Nelson
authors.forename: Magdalena I
authors.initials: MI
authors.lastname: Ivanova
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Sievers
authors.forename: Marcin I
authors.initials: MI
authors.lastname: Apostol
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thompson
authors.forename: Melinda
authors.initials: M
authors.lastname: Balbirnie
authors.forename: Jed J W
authors.initials: JJ
authors.lastname: Wiltzius
authors.forename: Heather T
authors.initials: HT
authors.lastname: McFarlane
authors.forename: Anders Ø
authors.initials: AØ
authors.lastname: Madsen
authors.forename: Christian
authors.initials: C
authors.lastname: Riekel
authors.forename: David
authors.initials: D
authors.lastname: Eisenberg
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D003460:Crystallization; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry*; D011328:Prions / Q000737:chemistry; D011487:Protein Conformation
chemical_list: D000682:Amyloid; D010446:Peptide Fragments; D011328:Prions