Supramolecular Structure in Full-Length Alzheimer's β-Amyloid Fibrils: Evidence for a Parallel β-Sheet Organization from Solid-State Nuclear Magnetic Resonance

Balbach, John J. (author): 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. (author): Laboratory of Chemical Physics, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, Bethesda, Maryland 20892-0520 USA

Oyler, Nathan A. (author): Laboratory of Chemical Physics, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, Bethesda, Maryland 20892-0520 USA

Antzutkin, Oleg (author): Luleå tekniska universitet,Industriell miljö- och processteknik

Gordon, David J. (author): Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois 60637 USA

Meredith, Stephen C. (author): Department of Pathology, The University of Chicago, Chicago, Illinois 60637 USA

Tycko, Robert (author): Laboratory of Chemical Physics, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, Bethesda, Maryland 20892-0520 USA

(creator_code:org_t)

Related links:: https://doi.org/10.1...; show more...; https://ltu.diva-por... (primary) (Raw object); https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Abstract Subject headings

We report constraints on the supramolecular structure of amyloid fibrils formed by the 40-residue β-amyloid peptide associated with Alzheimer's disease (Aβ1–40) obtained from solid-state nuclear magnetic resonance (NMR) measurements of intermolecular dipole-dipole couplings between 13C 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 13C magic-angle spinning NMR spectra of the labeled Aβ1–40 samples. The fpRFDR-CT data reveal nearest-neighbor intermolecular distances of 4.8 ± 0.5 Å for carbon sites from residues 12 through 39, indicating a parallel alignment of neighboring peptide chains in the predominantly β-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 Aβ1–40, including the first nine residues. These results place strong constraints on any molecular-level structural model for full-length β-amyloid fibrils.

By the author/editor: Balbach, John J.; Petkova, Aneta T ...; Oyler, Nathan A.; Antzutkin, Oleg; Gordon, David J.; Meredith, Stephe ...; show more...; Tycko, Robert; show less...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Chemical Science ...; and Physical Chemist ...

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