New role in cells suggested for ATP

Adenosine triphosphate (ATP) performs many jobs in a cell. It carries energy, serves as a signaling molecule, and is the source of adenosine in DNA and RNA.

But cells contain far more ATP—as much as 5 mM in the cytoplasm—than these known uses seem to require. That might be because ATP also can solubilize proteins, suggests a new study (Science 2017, DOI: 10.1126/science.aaf6846).

ATP has the general characteristics of a hydrotrope, an amphiphilic molecule that has both a hydrophilic and a hydrophobic component but does not assemble into structures such as micelles. Hydrotropes are used industrially to solubilize hydrophobic species in aqueous solution. The hydrophobic portion of hydrotropes—such as ATP’s adenosine—likely interacts with the hydrophobic species, while the hydrophilic part—such as ATP’s triphosphate—allows the species to stay in solution.

In the new work, a team led by Yamuna Krishnan of the University of Chicago and Anthony A. Hyman of the Max Planck Institute of Molecular Cell Biology & Genetics investigated the effects of ATP on the aggregation of several proteins. They found that ATP could prevent the aggregation of two proteins known to form amyloid clumps. For a third protein, ATP was further able to dissolve fibers of already aggregated protein. And ATP kept proteins in boiled egg white from aggregating.

“Most healthy cell functions require that proteins remain soluble at enormous intracellular concentrations, without aggregating into pathogenic deposits,” write Allyson M. Rice and Michael K. Rosen of the University of Texas Southwestern Medical Center in a perspective accompanying the paper. “The cell may exploit a natural hydrotrope to keep itself in a functioning, dynamic state.”

ATP may have also played an important role in the origin and evolution of life, Krishnan, Hyman, and colleagues note in their paper. Aggregation would have been a problem even for early biological macromolecules. “ATP may have been coopted early in evolution to prevent such aggregation,” even before the molecule became an energy carrier, the researchers suggest.