Atomic structures of amyloid cross-beta spines reveal varied steric zippers.
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.
Sawaya
Michael R
MR
Howard Hughes Medical Institute, UCLA-DOE Institute of Genomics and Proteomics, Los Angeles, California 90095-1570, USA.
Sambashivan
Shilpa
S
Nelson
Rebecca
R
Ivanova
Magdalena I
MI
Sievers
Stuart A
SA
Apostol
Marcin I
MI
Thompson
Michael J
MJ
Balbirnie
Melinda
M
Wiltzius
Jed J W
JJ
McFarlane
Heather T
HT
Madsen
Anders Ø
AØ
Riekel
Christian
C
Eisenberg
David
D
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
D000682:Amyloid; D010446:Peptide Fragments; D011328:Prions