ATP emerged to induce protein folding, inhibit aggregation and increase stability

By NMR characterization of effects of ATP and related molecules on the folding and dynamics of the ALS-causing C71G-PFN1 and nascent hSOD1, we reveal for the first time that ATP has a general capacity in inducing protein folding with the highest efficiency known so far. This capacity was further identified to result from triphosphate, a key intermediate in prebiotic chemistry, which, however, can severely trigger protein aggregation. Remarkably, by joining adenosine and triphosphate together, ATP integrates three abilities to simultaneously induce protein folding, inhibit aggregation and increase thermodynamic stability. Our study implies that the emergence of ATP might represent an irreplaceable step essential for the Origin of Life, and decrypts a principle for engineering small molecules with three functions to treat aggregation-associated ageing and diseases. One sentence summary By joining adenosine and triphosphate, ATP integrates three abilities to control protein homeostasis for the Origin of Life.