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ATP Kinetically Modulates Pathogenic Tau Fibrillations

submitted on 14.03.2020, 12:30 and posted on 16.03.2020, 12:00 by Jong Yoon Han,, Chae Eun Heo, Sungsu Lim, Jeeyoung Lee, Iryna Martsishevska, Dongjoon Im, Min Jae Lee, Yun Kyung Kim, Hugh I. Kim
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 abundant in the cytosol of cells, catalyses tau fibrillation via supramolecular complexation with basic residues of tau. Our results showed that ATP attracts multiple lysine residues of four-repeat domain of tau (K18), thereby immediately forming dimers which convert to nuclei to accelerate fibril elongation. However, ATP was not directly incorporated in the K18 fibrils suggesting a catalytic role of ATP in 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 change and fibrillation of tau.


National Research Foundation of Korea (2019R1A2C2086193)

NST of Korea (CRC-15-04-KIST)


Email Address of Submitting Author


Korea university


Republic of Korea

ORCID For Submitting Author


Declaration of Conflict of Interest

no conflict of interest