Kinetic Modulation of Amyloid-β (1-42) Aggregation and Toxicity by Structure-Based Rational Design

Dongjoon Im, Chae Eun Heo, Myung Kook Son, Chae Ri Park, Hugh I. Kim, Jeong Mo Choi

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Several point mutations can modulate protein structure and dynamics, leading to different natures. Especially in the case of amyloidogenic proteins closely related to neurodegenerative diseases, structural changes originating from point mutations can affect fibrillation kinetics. Herein, we rationally designed mutant candidates to inhibit the fibrillation process of amyloid-β with its point mutants through multistep in silico analyses. Our results showed that the designed mutants induced kinetic self-Assembly suppression and reduced the toxicity of the aggregate. A multidisciplinary biophysical approach with small-Angle X-ray scattering, ion mobility-mass spectrometry, mass spectrometry, and additional in silico experiments was performed to reveal the structural basis associated with the inhibition of fibril formation. The structure-based design of the mutants with suppressed self-Assembly performed in this study could provide a different perspective for modulating amyloid aggregation based on the structural understanding of the intrinsically disordered proteins.

Original languageEnglish
Pages (from-to)1603-1611
Number of pages9
JournalJournal of the American Chemical Society
Issue number4
Publication statusPublished - 2022 Feb 2

Bibliographical note

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© 2022 American Chemical Society. All rights reserved.

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


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