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PMID: 12124300 Published · ppublish English Journal Article

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

Biophysical journal ·Vol. 83 ·No. 2 ·2002-08-00 ·Pages 1205-16

Balbach JJ, Petkova AT, Oyler NA, Antzutkin ON, Gordon DJ, Meredith SC, Tycko R

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.

MeSH Terms
Alzheimer Disease/metabolism Amyloid beta-Peptides/chemistry,metabolism Carbon/chemistry Humans Magnetic Resonance Spectroscopy Peptide Biosynthesis Peptides/chemistry Protein Conformation Protein Structure, Secondary Protein Structure, Tertiary
Chemicals
Amyloid beta-Peptides Peptides Carbon
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Balbach John J
Laboratory of Chemical Physics, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, Bethesda, Maryland 20892-0520 USA.
Petkova Aneta T
Oyler Nathan A
Antzutkin Oleg N
Gordon David J
Meredith Stephen C
Tycko Robert
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Article Info
Journal
Biophysical journal
Abbr.
Biophys J
ISSN
0006-3495
DOI
10.1016/S0006-3495(02)75244-2
Published
2002-08-00
Pages
1205-16
Language
English
Region
United States
NLM ID
0370626
PMCID
PMC1302222
Subset
IM
External Links
PubMed source DOI: 10.1016/S0006-3495(02)75244-2 PMC Full Text View journal details
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