Multiple quantum solid-state NMR indicates a parallel, not antiparallel, organization of beta-sheets in Alzheimer's beta-amyloid fibrils.
Senile plaques associated with Alzheimer's disease contain deposits of fibrils formed by 39- to 43-residue beta-amyloid peptides with possible neurotoxic effects. X-ray diffraction measurements on oriented fibril bundles have indicated an extended beta-sheet structure for Alzheimer's beta-amyloid fibrils and other amyloid fibrils, but the supramolecular organization of the beta-sheets and other structural details are not well established because of the intrinsically noncrystalline, insoluble nature of amyloid fibrils. Here we report solid-state NMR measurements, using a multiple quantum (MQ) (13)C NMR technique, that probe the beta-sheet organization in fibrils formed by the full-length, 40-residue beta-amyloid peptide (Abeta(1-40)). Although an antiparallel beta-sheet organization often is assumed and is invoked in recent structural models for full-length beta-amyloid fibrils, the MQNMR data indicate an in-register, parallel organization. This work provides site-specific, atomic-level structural constraints on full-length beta-amyloid fibrils and applies MQNMR to a significant problem in structural biology.
Antzutkin
O N
ON
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA.
Balbach
J J
JJ
Leapman
R D
RD
Rizzo
N W
NW
Reed
J
J
Tycko
R
R
D000409:Alanine; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000648:ultrastructure; D019281:Dimerization; D006801:Humans; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000648:ultrastructure; D017433:Protein Structure, Secondary; D011789:Quantum Theory
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D000409:Alanine