Heterotypic Interactions between the 40- and 42-Residue Isoforms of β-Amyloid Peptides on Lipid Bilayer Surfaces

Co-aggregation involving different amyloidogenic sequences has been emphasized recently in the modified amyloid cascade hypothesis. Yet, molecular-level interactions between two predominant β-amyloid peptide sequences, Aβ and Aβ , in the fibrillation process in membrane-mimicked environments remain...

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Bibliographic Details
Published in:ACS chemical neuroscience 2023-12, Vol.14 (23), p.4153-4162
Main Authors: Qiang, Wei, Kengwerere, Maurine K, Zhao, Wancheng, Scott, Faith J, Wutoh-Hughes, Xyomara, Wang, Tuo, Mentink-Vigier, Frederic
Format: Article
Language:English
Subjects:
Alzheimer Disease
Amino Acid Sequence
Amyloid beta-Peptides - chemistry
Humans
Lipid Bilayers
Peptide Fragments - chemistry
Protein Isoforms
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Summary:Co-aggregation involving different amyloidogenic sequences has been emphasized recently in the modified amyloid cascade hypothesis. Yet, molecular-level interactions between two predominant β-amyloid peptide sequences, Aβ and Aβ , in the fibrillation process in membrane-mimicked environments remain unclear. Here, we report biophysical evidence that demonstrates the molecular-level interactions between Aβ and Aβ at the membrane-associated conucleation stage using dynamic nuclear polarization-enhanced solid-state NMR spectroscopy. These residue-specific contacts are distinguished from those reported in mature fibrils formed by either Aβ or Aβ . Meanwhile, site-specific interactions between Aβ and lipid molecules and modulation of microsecond-time-scale lipid dynamics are observed, which may be responsible for the more rapid and significant membrane content leakage compared to that with Aβ alone.
ISSN:1948-7193
1948-7193
DOI:10.1021/acschemneuro.3c00523