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

Nat Commun. 2019 Mar 11;10(1):1155. doi: 10.1038/s41467-019-09107-y.


Adenosine triphosphate (ATP) plays fundamental roles in cellular biochemistry and was recently discovered to function as a biological hydrotrope. Here, we use mass spectrometry to interrogate ATP-mediated regulation of protein thermal stability and protein solubility on a proteome-wide scale. Thermal proteome profiling reveals high affinity interactions of ATP as a substrate and as an allosteric modulator that has widespread influence on protein complexes and their stability. Further, we develop a strategy for proteome-wide solubility profiling, and discover ATP-dependent solubilization of at least 25% of the insoluble proteome. ATP increases the solubility of positively charged, intrinsically disordered proteins, and their susceptibility for solubilization varies depending on their localization to different membrane-less organelles. Moreover, a few proteins, exhibit an ATP-dependent decrease in solubility, likely reflecting polymer formation. Our data provides a proteome-wide, quantitative insight into how ATP influences protein structure and solubility across the spectrum of physiologically relevant concentrations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Adenosine Triphosphate / metabolism*
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism
  • Humans
  • Jurkat Cells
  • Mass Spectrometry
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism
  • Protein Binding
  • Protein Stability
  • Proteome / chemistry
  • Proteome / metabolism*
  • Proteomics / methods
  • Solubility


  • BANF1 protein, human
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Proteome
  • Adenosine Triphosphate
  • DNA