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Metastable Alpha-rich and Beta-rich Conformations of Small Aβ42 Peptide Oligomers
  • Philippe Derreumaux,
  • Phuong Nguyen,
  • Fabio Sterpone
Philippe Derreumaux
Institut de Biologie Physico-Chimique

Corresponding Author:[email protected]

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Phuong Nguyen
Institut de Biologie Physico-Chimique
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Fabio Sterpone
Institut de Biologie Physico-Chimique
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Probing the structures of amyloid-beta (Aβ) peptides in the early steps of aggregation is extremely difficult experimentally and computationally. Yet, this knowledge is extremely important as small oligomers are the most toxic species. Experiments and simulations on Aβ42 monomer point to random coil conformations with either transient helical or β-strand content. Our current conformational description of small Aβ42 oligomers is funneled toward amorphous aggregates with some β-sheet content and rare excited states with well-ordered assemblies of β-sheets. In this study, we emphasize another view based on metastable α-helix bundle oligomers spanning the C-terminus residues which are predicted by the machine-learning AlphaFold2 method and supported indirectly by low-resolution experimental data on many amyloid polypeptides. This finding has consequences in designing drugs to reduce aggregation and toxicity.
15 Dec 2022Submitted to PROTEINS: Structure, Function, and Bioinformatics
15 Dec 2022Submission Checks Completed
15 Dec 2022Assigned to Editor
15 Dec 2022Review(s) Completed, Editorial Evaluation Pending
06 Jan 2023Reviewer(s) Assigned
08 Feb 2023Editorial Decision: Revise Minor
16 Feb 20231st Revision Received
17 Feb 2023Submission Checks Completed
17 Feb 2023Assigned to Editor
17 Feb 2023Review(s) Completed, Editorial Evaluation Pending
13 Mar 2023Reviewer(s) Assigned
23 Mar 2023Editorial Decision: Accept