The Formation Mechanism of Segmented Ring-Shaped Aβ Oligomers and Protofibrils

Hyunsung Choi, Wonseok Lee, Gyudo Lee, Dae Sung Yoon, Sungsoo Na

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


A clear understanding of amyloid formation with diverse morphologies is critical to overcoming the fatal disease amyloidosis. Studies have revealed that monomer concentration is a crucial factor for determining amyloid morphologies, such as protofibrils, annular, or spherical oligomers. However, gaining a complete understanding of the mechanism of formation of the various amyloid morphologies has been limited by the lack of experimental devices and insufficient knowledge. In this study, we demonstrate that the monomer concentration is an essential factor in determining the morphology of beta-amyloid (Aβ) oligomers or protofibrils. By computational and experimental approaches, we investigated the strategies for structural stabilization of amyloid protein, the morphological changes, and amyloid aggregation. In particular, we found unprecedented conformations, e.g., single bent oligomers and segmented ring-shaped protofibrils, the formation of which was explained by the computational analysis. Our findings provide insight into the structural features of amyloid molecules formed at low concentrations of monomer, which will help determine the clinical targets (in therapy) to effectively inhibit amyloid formation in the early stages of the amyloid growth phase.

Original languageEnglish
Pages (from-to)3830-3838
Number of pages9
JournalACS Chemical Neuroscience
Issue number8
Publication statusPublished - 2019 Aug 21

Bibliographical note

Funding Information:
Dae Sung Yoon gratefully acknowledges the Basic Science Research Program, through the National Research Foundation of Korea (NRF, Grant no. 2019R1A2B5B01070617, and NRF, Grant no. 2018M3C1B7020722).

Publisher Copyright:
© 2019 American Chemical Society.


  • atomic force microscopy
  • beta-amyloid
  • molecular dynamics
  • p3 peptide
  • segmented ring-shaped structure

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology


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