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

Mohtadin Hashemi; Yuliang Zhang; Zhengjian Lv; Yuri L. Lyubchenko

doi:10.1039/c9na00380k

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

Mohtadin Hashemi, Yuliang Zhang, Zhengjian Lv, Yuri L. Lyubchenko

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8 Scopus citations

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.

Original language	English (US)
Pages (from-to)	3892-3899
Number of pages	8
Journal	Nanoscale Advances
Volume	1
Issue number	10
DOIs	https://doi.org/10.1039/c9na00380k
State	Published - 2019

ASJC Scopus subject areas

Engineering(all)
Bioengineering
Atomic and Molecular Physics, and Optics
Materials Science(all)
Chemistry(all)

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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.",

author = "Mohtadin Hashemi and Yuliang Zhang and Zhengjian Lv and Lyubchenko, {Yuri L.}",

note = "Funding Information: This work was supported by NIH grants GM096039 and GM100156, NSF grant 1004094, and the PSCA14025P award for computer time on Anton at Pittsburgh Supercomputing Center (PSC) – all to YLL. MH was supported by the Bukey Memorial Fellowship. Computational modeling was performed using facilities of the Holland Computing Center at the University of Nebraska (supported by the Nebraska Research Initiative) and the San Diego Supercomputing Center at the University of California San Diego through the Extreme Science and Engineering Discovery Environment (XSEDE; supported by National Science Foundation [ACI-1053575 for XSEDE]). Anton computer time was provided by the PSC through Grant R01GM116961 from the NIH. The Anton machine at PSC was generously made available by D. E. Shaw Research. We thank Dr Yuguang Mu for providing the dPCA Fortran program. Publisher Copyright: {\textcopyright} 2019 The Royal Society of Chemistry.",

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doi = "10.1039/c9na00380k",

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N1 - Funding Information: This work was supported by NIH grants GM096039 and GM100156, NSF grant 1004094, and the PSCA14025P award for computer time on Anton at Pittsburgh Supercomputing Center (PSC) – all to YLL. MH was supported by the Bukey Memorial Fellowship. Computational modeling was performed using facilities of the Holland Computing Center at the University of Nebraska (supported by the Nebraska Research Initiative) and the San Diego Supercomputing Center at the University of California San Diego through the Extreme Science and Engineering Discovery Environment (XSEDE; supported by National Science Foundation [ACI-1053575 for XSEDE]). Anton computer time was provided by the PSC through Grant R01GM116961 from the NIH. The Anton machine at PSC was generously made available by D. E. Shaw Research. We thank Dr Yuguang Mu for providing the dPCA Fortran program. Publisher Copyright: © 2019 The Royal Society of Chemistry.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

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

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