Univ. of California, Irvine, CA (United States); King Abdulaziz Univ., Jeddah (Saudi Arabia)
King Abdulaziz Univ., Jeddah (Saudi Arabia)
Univ. de Lyon, Lyon (France)
Eidgenossische Technische Hochschule Zurich, Zurich (Switzerland); Goethe Univ. Frankfurt am Main, Frankfurt am Main (Germany); Tokyo Metropolitan Univ., Tokyo (Japan)
Amyloid-β (Aβ) is present in humans as a 39- to 42-amino acid residue metabolic product of the amyloid precursor protein. Although the two predominant forms, Aβ(1–40) and Aβ(1–42), differ in only two residues, they display different biophysical, biological, and clinical behavior. Aβ(1–42) is the more neurotoxic species, aggregates much faster, and dominates in senile plaque of Alzheimer’s disease (AD) patients. Although small Aβ oligomers are believed to be the neurotoxic species, Aβ amyloid fibrils are, because of their presence in plaques, a pathological hallmark of AD and appear to play an important role in disease progression through cell-to-cell transmissibility. Here, we solved the 3D structure of a disease-relevant Aβ(1–42) fibril polymorph, combining data from solid-state NMR spectroscopy and mass-per-length measurements from EM. The 3D structure is composed of two molecules per fibril layer, with residues 15–42 forming a double-horseshoe–like cross–β-sheet entity with maximally buried hydrophobic side chains. Lastly, residues 1–14 are partially ordered and in a β-strand conformation, but do not display unambiguous distance restraints to the remainder of the core structure.
Wälti, Marielle Aulikki, et al. "Atomic-resolution structure of a disease-relevant Aβ(1–42) amyloid fibril." Proceedings of the National Academy of Sciences of the United States of America, vol. 113, no. 34, Jul. 2016. https://doi.org/10.1073/pnas.1600749113
Wälti, Marielle Aulikki, Ravotti, Francesco, Arai, Hiromi, Glabe, Charles G., Wall, Joseph S., Böckmann, Anja, Güntert, Peter, Meier, Beat H., & Riek, Roland (2016). Atomic-resolution structure of a disease-relevant Aβ(1–42) amyloid fibril. Proceedings of the National Academy of Sciences of the United States of America, 113(34). https://doi.org/10.1073/pnas.1600749113
Wälti, Marielle Aulikki, Ravotti, Francesco, Arai, Hiromi, et al., "Atomic-resolution structure of a disease-relevant Aβ(1–42) amyloid fibril," Proceedings of the National Academy of Sciences of the United States of America 113, no. 34 (2016), https://doi.org/10.1073/pnas.1600749113
@article{osti_1351799,
author = {Wälti, Marielle Aulikki and Ravotti, Francesco and Arai, Hiromi and Glabe, Charles G. and Wall, Joseph S. and Böckmann, Anja and Güntert, Peter and Meier, Beat H. and Riek, Roland},
title = {Atomic-resolution structure of a disease-relevant Aβ(1–42) amyloid fibril},
annote = {Amyloid-β (Aβ) is present in humans as a 39- to 42-amino acid residue metabolic product of the amyloid precursor protein. Although the two predominant forms, Aβ(1–40) and Aβ(1–42), differ in only two residues, they display different biophysical, biological, and clinical behavior. Aβ(1–42) is the more neurotoxic species, aggregates much faster, and dominates in senile plaque of Alzheimer’s disease (AD) patients. Although small Aβ oligomers are believed to be the neurotoxic species, Aβ amyloid fibrils are, because of their presence in plaques, a pathological hallmark of AD and appear to play an important role in disease progression through cell-to-cell transmissibility. Here, we solved the 3D structure of a disease-relevant Aβ(1–42) fibril polymorph, combining data from solid-state NMR spectroscopy and mass-per-length measurements from EM. The 3D structure is composed of two molecules per fibril layer, with residues 15–42 forming a double-horseshoe–like cross–β-sheet entity with maximally buried hydrophobic side chains. Lastly, residues 1–14 are partially ordered and in a β-strand conformation, but do not display unambiguous distance restraints to the remainder of the core structure.},
doi = {10.1073/pnas.1600749113},
url = {https://www.osti.gov/biblio/1351799},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
issn = {ISSN 0027-8424},
number = {34},
volume = {113},
place = {United States},
publisher = {National Academy of Sciences, Washington, DC (United States)},
year = {2016},
month = {07}}
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
OSTI ID:
1351799
Report Number(s):
BNL--113696-2017-JA
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 34 Vol. 113; ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)Copyright Statement