Abstract
Proteins occurring in significantly high concentrations in cellular environments (over 100 mg/mL) and functioning in crowded cytoplasm, often face the prodigious challenges of aggregation which are the pathological hallmark of aging and are critically responsible for a wide spectrum of rising human diseases. Here we combine a joint-venture of complementary wet-lab experiment and molecular simulation to discern the potential ability of adenosine triphosphate (ATP) as solubilizer of protein aggregates. We show that ATP prevents both condensation of aggregation-prone intrinsically disordered protein Aβ40 and promotes dissolution of pre-formed aggregates. Computer simulation links ATP’s solubilizing role to its ability to modulate protein’s structural plasticity by unwinding protein conformation. We show that ATP is positioned as a superior biological solubilizer of protein aggregates over traditional chemical hydrotropes, potentially holding promises in therapeutic interventions in protein-aggregation related diseases. Going beyond its conventional activity as energy currency, the amphiphilic nature of ATP enables its protein-specific interaction that would enhance ATP’s efficiency in cellular processes.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Email: jmondal{at}tifrh.res.in Phone:+91-40-2020-3091
The manuscript has been updated with additional investigations and analysis.
