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Spontaneous self-assembly of amyloid β (1–40) into dimers

Journal Article · · Nanoscale Advances
DOI:https://doi.org/10.1039/c9na00380k· OSTI ID:1661023
 [1];  [2];  [3];  [1]
  1. Univ. of Nebraska Medical Center, Omaha, NE (United States)
  2. Univ. of Nebraska Medical Center, Omaha, NE (United States); Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
  3. Univ. of Nebraska Medical Center, Omaha, NE (United States); Bruker Nano Surfaces Division, Santa Barbara, CA (United States)
The self-assembly and fibrillation of amyloid β (Aβ) proteins is the neuropathological hallmark of Alzheimer's disease. However, the molecular mechanism of how disordered monomers assemble into aggregates remains largely unknown. In this work, we characterize the assembly of Aβ (1–40) monomers into dimers using long-time molecular dynamics simulations. Upon interaction, the monomers undergo conformational transitions, accompanied by change of the structure, leading to the formation of a stable dimer. The dimers are stabilized by interactions in the N-terminal region (residues 5–12), in the central hydrophobic region (residues 16–23), and in the C-terminal region (residues 30–40); with inter-peptide interactions focused around the N- and C-termini. The dimers do not contain long β-strands that are usually found in fibrils.
Research Organization:
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
Sponsoring Organization:
National Institutes of Health (NIH); National Science Foundation (NSF); USDOE National Nuclear Security Administration (NNSA)
Grant/Contract Number:
AC52-07NA27344
OSTI ID:
1661023
Report Number(s):
LLNL-JRNL--813715; 1021710
Journal Information:
Nanoscale Advances, Journal Name: Nanoscale Advances Journal Issue: 10 Vol. 1; ISSN 2516-0230
Publisher:
Royal Society of ChemistryCopyright Statement
Country of Publication:
United States
Language:
English

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