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bioRxiv · 10.1101/2024.01.15.575740

ATP Prevents Aggregation of Protein via Modulating its Monomeric Conformation

Sarkar, S.·Gupta, S.·Mahato, C.·Das, D.·Mondal, J.
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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 A{beta}40 and promotes dissolution of pre-formed aggregates. Computer simulation links ATPs solubilizing role to its ability to modulate proteins 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 ATPs efficiency in cellular processes.

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Sarkar, S., Gupta, S., Mahato, C., Das, D., Mondal, J.. 2024-01-16. ATP Prevents Aggregation of Protein via Modulating its Monomeric Conformation. https://doi.org/10.1101/2024.01.15.575740

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