Please use this identifier to cite or link to this item: https://doi.org/10.1038/s42003-021-02247-2
Title: ATP biphasically modulates LLPS of TDP-43 PLD by specifically binding arginine residues
Authors: Dang, Mei 
Lim, Liangzhong 
Kang, Jian
Song, Jianxing 
Issue Date: 10-Jun-2021
Publisher: Nature Research
Citation: Dang, Mei, Lim, Liangzhong, Kang, Jian, Song, Jianxing (2021-06-10). ATP biphasically modulates LLPS of TDP-43 PLD by specifically binding arginine residues. Communications Biology 4 (1) : 714. ScholarBank@NUS Repository. https://doi.org/10.1038/s42003-021-02247-2
Rights: Attribution 4.0 International
Abstract: Mysteriously neurons maintain ATP concentrations of ~3 mM but whether ATP modulates TDP-43 LLPS remains completely unexplored. Here we characterized the effect of ATP on LLPS of TDP-43 PLD and seven mutants by DIC and NMR. The results revealed: 1) ATP induces and subsequently dissolves LLPS of TDP-43 PLD by specifically binding Arg saturated at 1:100. 2) ATP modifies the conformation-specific electrostatic property beyond just imposing screening effect. 3) Reversibility of LLPS of TDP-43 PLD and further exaggeration into aggregation appear to be controlled by a delicate network composed of both attractive and inhibitory interactions. Results together establish that ATP might be a universal but specific regulator for most, if not all, R-containing intrinsically-disordered regions by altering physicochemical properties, conformations, dynamics, LLPS and aggregation. Under physiological conditions, TDP-43 is highly bound with ATP and thus inhibited for LLPS, highlighting a central role of ATP in cell physiology, pathology and aging. © 2021, The Author(s).
Source Title: Communications Biology
URI: https://scholarbank.nus.edu.sg/handle/10635/233050
ISSN: 2399-3642
DOI: 10.1038/s42003-021-02247-2
Rights: Attribution 4.0 International
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