2019/03/11 by Sindhuja Sridharan, Nils Kurzawa, Thilo Werner +5 · 1 citation
Chemistry · Biochemistry, Genetics and Molecular Biology · #Mass Spectrometry Techniques and Applications #Protein Structure and Dynamics #Advanced Proteomics Techniques and Applications
paper · pdf · doi:10.1038/s41467-019-09107-y
openalex publication_date 2019/03/11 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/29
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.