Multiple quantum solid-state NMR indicates a parallel, not antiparallel, organization of beta-sheets in Alzheimer's beta-amyloid fibrils.

O N Antzutkin; J J Balbach; R D Leapman; N W Rizzo; J Reed; R Tycko

doi:10.1073/pnas.230315097

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Multiple quantum solid-state NMR indicates a parallel, not antiparallel, organization of beta-sheets in Alzheimer's beta-amyloid fibrils.

O N Antzutkin·J J Balbach·R D Leapman·N W Rizzo·J Reed·R Tycko

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Abstract

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.

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Alanine Amino Acid Sequence Amyloid beta-Peptides Dimerization Humans Molecular Sequence Data Nuclear Magnetic Resonance, Biomolecular Peptide Fragments Protein Structure, Secondary Quantum Theory Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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O N Antzutkin, J J Balbach, R D Leapman, N W Rizzo, J Reed, R Tycko. 2000-11-21. Multiple quantum solid-state NMR indicates a parallel, not antiparallel, organization of beta-sheets in Alzheimer's beta-amyloid fibrils.. https://doi.org/10.1073/pnas.230315097

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