Open AccessAmyloid-β peptide dimers undergo a random coil to β-sheet transition in the aqueous phase but not at the neuronal membrane
Author(s) -
Hebah Fatafta,
Mohammed Khaled,
Michael C. Owen,
Abdallah Sayyed-Ahmad,
Birgit Strodel
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2106210118
Subject(s) - oligomer , random coil , biophysics , chemistry , membrane , p3 peptide , amyloid (mycology) , lipid bilayer , peptide , biochemistry , alzheimer's disease , amyloid precursor protein , biology , circular dichroism , medicine , inorganic chemistry , disease , pathology , organic chemistry
Significance The aggregation of the amyloid-β peptide (Aβ ) into neurotoxic oligomers is central to the development of Alzheimer’s disease. One possible source of their toxicity results from interactions of the Aβ oligomers with the neuronal membrane, damaging membrane integrity and thus neurons. However, molecular details of these interactions are unclear. Here, we contrast the dimerization of Aβ in solution and at the neuronal membrane. Our results clearly indicate that the sugar moieties of GM1 sequester Aβ by forming key hydrogen bonds with the peptide, which diverts the configuration of the Aβ dimers away from damagingβ -sheet–rich structures. These findings underline the importance of GM1 in Alzheimer’s disease progression and provide a nanoscopic basis for its reported neuroprotective effect.