ATP kinetically modulates pathogenic tau fibrillations

Hugh I. Kim, Chae Eun Heo, Jong Yoon Han, Sungsu Lim, Jeeyoung Lee, Dongjoon Im, Min Jae Lee, Yun Kyung Kim

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Advanced understanding of Alzheimer's disease (AD) and several tauopathies over the past decades indicates the pathological importance of tau aggregation in these diseases. Herein, we demonstrated that adenosine triphosphate (ATP), a highly charged anionic molecule found abundantly in the cytosol of cells, catalyzes fibrillation of tau as well as human islet amyloid polypeptide, a representative of basic intrinsically disordered proteins. Our results showed that ATP attracts multiple lysine residues of the four-repeat domain of tau (K18) via supramolecular complexation, thereby forming dimers that are converted to nuclei and accelerate fibril elongation. However, ATP was not directly incorporated into the K18 fibrils, suggesting that ATP plays the role of a catalyst, rather than a reactant, during K18 fibrillation. We also characterized the correlation between ATP dyshomeostasis and tau aggregation in the cellular environment. Our multiple biophysical approaches, including native mass spectrometry (MS), small-angle X-ray scattering (SAXS), and molecular dynamics (MD) simulation, provided insights into the molecular-level influence of ATP on the structural changes and fibrillation of tau.

Original languageEnglish
Pages (from-to)3144-3152
Number of pages9
JournalACS Chemical Neuroscience
Issue number19
Publication statusPublished - 2020 Oct 7

Bibliographical note

Publisher Copyright:
© 2020 American Chemical Society.


  • Amyloid fibrillation
  • Amyloidogenic proteins
  • Biophysics
  • Mass spectrometry
  • Small-angle X-ray scattering
  • Tau

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology


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