ATP as a biological hydrotrope

@article{Patel2017ATPAA,
  title={ATP as a biological hydrotrope},
  author={Avinash B. Patel and Liliana Malinovska and Shambaditya Saha and Jie Wang and Simon Alberti and Yamuna Krishnan and Anthony A. Hyman},
  journal={Science},
  year={2017},
  volume={356},
  pages={753 - 756}
}
ATP boosts protein solubility Adenosine triphosphate (ATP) has well-characterized roles in providing energy for biochemical reactions within cells. Patel et al. find that ATP may also enhance protein solubility, which could help explain why such high concentrations of ATP are maintained in cells (see the Perspective by Rice and Rosen). Protein concentrations in cells can exceed 100 mg/ml. The authors found that ATP at concentrations found in cells could act as a hydrotrope to help solubilize… 

Mechanistic Insights on ATP’s role as Hydrotrope

Computer simulations of prototypical macromolecules in aqueous ATP solution are designed to dissect the molecular mechanism underlying ATP’s newly discovered role as a hydrotrope to provide fresh mechanistic insights into the dual solubilizing and denaturing abilities of ATP.

Mechanistic Insights on ATP's Role as a Hydrotrope.

Computer simulations of prototypical macromolecules in aqueous ATP solution are designed to dissect the molecular mechanism underlying ATP's newly discovered role as a hydrotrope and renders evidence that the key to the ATP's superior hydrotropic role may lie in its inherent self-aggregation propensity.

Molecular Mechanism of Hydrotropic Properties of GTP and ATP.

Comparisons of the hydrotropic behavior of all four biological nucleoside triphosphates (NTPs) using molecular dynamics (MD) simulations can have broad implications for hydrotrope design in the pharmaceutical industry, as well as the possibility of cells employing GTP as a hydrot rope to regulate the hydrophobic protein aggregation in membrane-less biological condensates.

ATP Can Efficiently Stabilize Protein through a Unique Mechanism

Both ATP binding and the considerable improvement of thermal stability of ATP-bound protein were verified by experiments and the ultrahigh efficiency of ATP suggests a unique mechanism that is fundamentally different from previous models of cosolvents.

ATP controls the crowd

A previously unknown function for ATP is proposed in maintaining protein solubility and preventing macromolecular aggregation and it is shown that at physiologic concentrations (2 to 8 mM), the physical properties of ATP alone enable it to dissolve liquid-liquid phase- separated droplets and amyloid fibers.

Effects of Weak Nonspecific Interactions with ATP on Proteins.

Although the observed ATP-protein interaction was relatively weak overall, the high ratio of ATP to proteins in cells suggests that most proteins are likely to encounter transient interactions with ATP (and chemically similar metabolites) that confer metabolite-mediated protein surface protection.

Impact of the Cellular Environment on Adenosine Triphosphate Conformations.

Analysis of the all-atom model of a small volume of the Escherichia coli cytoplasm when contrasted with ATP modeled in vitro or resolved with protein structures deposited in the Protein Data Bank reveals that ATP molecules bound to proteins in cell form specific pitched conformations that are not observed at significant concentrations in the other environments.

Mechanistic Insight on General Protein-Binding Ability of ATP and the Impacts of Arginine Residues.

This work used molecular dynamics simulation to study the binding of ATPs to three proteins with distinct net charges and suggests that ATP tightly binds to Arg with high affinity, and Arg dominates the direct binding of ATP.

Dual roles for ATP in the regulation of phase separated protein aggregates in Xenopus oocyte nucleoli

It is shown that hydrotropic solubilization of nucleolar aggregates is preceded by a destabilizing event, and that ATP has dual roles in the maintenance of protein solubility.
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