DOI: 10.1101/488163Dec 5, 2018Paper

Proteome-wide solubility and thermal stability profiling reveals distinct regulatory roles for ATP

BioRxiv : the Preprint Server for Biology
Sindhuja SridharanMikhail M Savitski


Nucleotide triphosphates (NTPs) regulate numerous biochemical processes in cells as (co-)substrates, allosteric modulators, biosynthetic precursors, and signaling molecules. Apart from its roles as energy source fueling cellular biochemistry, adenosine triphosphate (ATP), the most abundant NTP in cells, has been reported to affect macromolecular assemblies, such as protein complexes and membrane-less organelles. Moreover, both ATP and guanosine triphosphate (GTP) have recently been shown to dissolve protein aggregates. However, system-wide studies to characterize NTP- interactions under conditions approximating the native cellular environment are lacking, which limits our perspective of the diverse physiological roles of NTPs. Here, we have mapped and quantified proteome-wide NTP-interactions by assessing thermal stability and solubility of proteins using mechanically disrupted cells. Our results reveal diverse biological roles of ATP depending on its concentration. We found that ATP specifically interacts with proteins that utilize it as substrate or allosteric modulator at doses lower than 500 μM, while it affects protein-protein interactions of protein complexes at mildly higher concentrations (between 1-2 mM). At high conce...Continue Reading

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