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

Abstract

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.

Authors:
ORCiD logo [1];  [2];  [3]; ORCiD logo [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)
Publication Date:
Research Org.:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Org.:
USDOE National Nuclear Security Administration (NNSA); National Institutes of Health (NIH); National Science Foundation (NSF)
OSTI Identifier:
1661023
Report Number(s):
LLNL-JRNL-813715
Journal ID: ISSN 2516-0230; 1021710
Grant/Contract Number:  
AC52-07NA27344; GM096039; GM100156; 1004094; ACI-1053575; R01GM116961
Resource Type:
Accepted Manuscript
Journal Name:
Nanoscale Advances
Additional Journal Information:
Journal Volume: 1; Journal Issue: 10; Journal ID: ISSN 2516-0230
Publisher:
Royal Society of Chemistry
Country of Publication:
United States
Language:
English
Subject:
biological and medical sciences

Citation Formats

Hashemi, Mohtadin, Zhang, Yuliang, Lv, Zhengjian, and Lyubchenko, Yuri L. Spontaneous self-assembly of amyloid β (1–40) into dimers. United States: N. p., 2019. Web. doi:10.1039/c9na00380k.
Hashemi, Mohtadin, Zhang, Yuliang, Lv, Zhengjian, & Lyubchenko, Yuri L. Spontaneous self-assembly of amyloid β (1–40) into dimers. United States. doi:10.1039/c9na00380k.
Hashemi, Mohtadin, Zhang, Yuliang, Lv, Zhengjian, and Lyubchenko, Yuri L. Tue . "Spontaneous self-assembly of amyloid β (1–40) into dimers". United States. doi:10.1039/c9na00380k. https://www.osti.gov/servlets/purl/1661023.
@article{osti_1661023,
title = {Spontaneous self-assembly of amyloid β (1–40) into dimers},
author = {Hashemi, Mohtadin and Zhang, Yuliang and Lv, Zhengjian and Lyubchenko, Yuri L.},
abstractNote = {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.},
doi = {10.1039/c9na00380k},
journal = {Nanoscale Advances},
number = 10,
volume = 1,
place = {United States},
year = {2019},
month = {9}
}

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