Kinase-phosphatase cycles drive self-sustained oscillations of protein condensates
- 1Johannes Gutenberg University Mainz
Abstract
Phase-separated protein condensates organize biochemical processes in cells. ATP-driven enzymatic reactions can change the physical properties and even trigger the dissolution of such condensates. Here we use molecular simulations to show how ATP-driven kinase and phosphatase reactions modulate the organization of TDP-43 low complexity domain (LCD) condensates. TDP-43 phosphorylation is enhanced by condensation, as CK1{delta} preferentially binds to and acts in TDP-43 LCD condensates, whereas dephosphorylation by the phosphatase calcineurin occurs predominantly in the dilute phase. This differential recruitment of kinases and phosphatases, together with the slow redistribution of kinases into newly formed condensates, triggers oscillatory appearance and disappearance of TDP-43 LCD condensates. The oscillations are self-sustained, persisting at constant chemical driving, showing that an antagonistic kinase-phosphatase pair can endow a condensate with autonomous dynamics rather than only setting its structure.
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BibTeX
@misc{zippo2026kinasephosphatase,
title = {{Kinase-phosphatase cycles drive self-sustained oscillations of protein condensates}},
author = {E. Zippo and L. Qiao and D. Dormann and T. Speck and F. Schmid and L. S. Stelzl},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.27.762139},
url = {https://www.biorxiv.org/content/10.64898/2026.10.27.762139v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Kinase-phosphatase cycles drive self-sustained oscillations of protein condensates
AU - E. Zippo
AU - L. Qiao
AU - D. Dormann
AU - T. Speck
AU - F. Schmid
AU - L. S. Stelzl
PY - 2026
DA - 2026/10/27
PB - bioRxiv
DO - 10.64898/2026.10.27.762139
UR - https://www.biorxiv.org/content/10.64898/2026.10.27.762139v1
AB - Phase-separated protein condensates organize biochemical processes in cells. ATP-driven enzymatic reactions can change the physical properties and even trigger the dissolution of such condensates. Here we use molecular simulations to show how ATP-driven kinase and phosphatase reactions modulate the organization of TDP-43 low complexity domain (LCD) condensates. TDP-43 phosphorylation is enhanced by condensation, as CK1{delta} preferentially binds to and acts in TDP-43 LCD condensates, whereas dephosphorylation by the phosphatase calcineurin occurs predominantly in the dilute phase. This differential recruitment of kinases and phosphatases, together with the slow redistribution of kinases into newly formed condensates, triggers oscillatory appearance and disappearance of TDP-43 LCD condensates. The oscillations are self-sustained, persisting at constant chemical driving, showing that an antagonistic kinase-phosphatase pair can endow a condensate with autonomous dynamics rather than only setting its structure.
ER -