Supramolecular structure in full-length Alzheimer's beta-amyloid fibrils: evidence for a parallel beta-sheet organization from solid-state nuclear magnetic resonance

John J Balbach; Aneta T Petkova; Nathan A Oyler; Oleg N Antzutkin; David J Gordon; Stephen C Meredith; Robert Tycko

doi:10.1016/S0006-3495(02)75244-2

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Supramolecular structure in full-length Alzheimer's beta-amyloid fibrils: evidence for a parallel beta-sheet organization from solid-state nuclear magnetic resonance

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Supramolecular structure in full-length Alzheimer's beta-amyloid fibrils: evidence for a parallel beta-sheet organization from solid-state nuclear magnetic resonance

John J Balbach, Aneta T Petkova, Nathan A Oyler, Oleg N Antzutkin, David J Gordon, Stephen C Meredith and Robert Tycko

Biophysical journal, Vol.83(2), pp.1205-1216

08/2002

DOI: 10.1016/S0006-3495(02)75244-2

PMCID: PMC1302222

PMID: 12124300

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Abstract

We report constraints on the supramolecular structure of amyloid fibrils formed by the 40-residue beta-amyloid peptide associated with Alzheimer's disease (A beta(1-40)) obtained from solid-state nuclear magnetic resonance (NMR) measurements of intermolecular dipole-dipole couplings between (13)C labels at 11 carbon sites in residues 2 through 39. The measurements are carried out under magic-angle spinning conditions, using the constant-time finite-pulse radiofrequency-driven recoupling (fpRFDR-CT) technique. We also present one-dimensional (13)C magic-angle spinning NMR spectra of the labeled A beta(1-40) samples. The fpRFDR-CT data reveal nearest-neighbor intermolecular distances of 4.8 +/- 0.5 A for carbon sites from residues 12 through 39, indicating a parallel alignment of neighboring peptide chains in the predominantly beta-sheet structure of the amyloid fibrils. The one-dimensional NMR spectra indicate structural order at these sites. The fpRFDR-CT data and NMR spectra also indicate structural disorder in the N-terminal segment of A beta(1-40), including the first nine residues. These results place strong constraints on any molecular-level structural model for full-length beta-amyloid fibrils.

Protein Structure, Tertiary

Peptide Biosynthesis

Magnetic Resonance Spectroscopy

Peptides - chemistry

Protein Structure, Secondary

Humans

Alzheimer Disease - metabolism

Amyloid beta-Peptides - metabolism

Protein Conformation

Amyloid beta-Peptides - chemistry

Carbon - chemistry

Details

Title: Subtitle: Supramolecular structure in full-length Alzheimer's beta-amyloid fibrils: evidence for a parallel beta-sheet organization from solid-state nuclear magnetic resonance
Creators: John J Balbach - Laboratory of Chemical Physics, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, Bethesda, Maryland 20892-0520 USA
Aneta T Petkova
Nathan A Oyler
Oleg N Antzutkin
David J Gordon
Stephen C Meredith
Robert Tycko
Resource Type: Journal article
Publication Details: Biophysical journal, Vol.83(2), pp.1205-1216
DOI: 10.1016/S0006-3495(02)75244-2
PMID: 12124300
PMCID: PMC1302222
ISSN: 0006-3495
eISSN: 1542-0086
Language: English
Date published: 08/2002
Academic Unit: Stead Family Department of Pediatrics; Hematology/Oncology
Record Identifier: 9984093602402771

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