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Effects of Weak Nonspecific Interactions with ATP on Proteins
- Source :
- Journal of the American Chemical Society. 143(31)
- Publication Year :
- 2021
-
Abstract
- Adenosine triphosphate (ATP) is an immensely well-studied metabolite serving multiple key biochemical roles as the major chemical energy currency in living systems, a building block of ribonucleic acids, and a phosphoryl group donor in kinase-mediated signaling. Intriguingly, ATP has been recently proposed to act as a hydrotrope that inhibits aggregation of amyloidogenic proteins; however, the underlying mechanism and the general physicochemical effect that coexistence with ATP exerts on proteins remain unclear. By combining NMR spectroscopy and MD simulations, here we observed weak but unambiguously measurable and concentration-dependent noncovalent interactions between ATP and various proteins. The interactions were most pronounced for an intrinsically disordered protein (α-synuclein) and for residues in flexible regions (e.g., loops or termini) of two representative folded proteins (ubiquitin and the dimeric ubiquitin-binding domain of p62). As shown by solution NMR, a consequence of the ATP-protein interaction was altered hydration of solvent-exposed residues in the protein. The observation that ATP interacted with all three proteins suggests that ATP is a general nonspecific binder of proteins. Several complementary biophysical methods further confirmed that, at physiological concentrations of ∼5-10 mM, ATP starts to form oligomeric states via magnesium-chelating and chelation-independent mechanisms, in agreement with previous studies. Although the observed ATP-protein interaction was relatively weak overall, the high ratio of ATP (monomeric free ATP, mono- and divalent ion-bound ATP, oligomeric and chelated 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.
- Subjects :
- chemistry.chemical_classification
Binding Sites
Magnetic Resonance Spectroscopy
biology
Ubiquitin
Metabolite
General Chemistry
Nuclear magnetic resonance spectroscopy
Molecular Dynamics Simulation
Biochemistry
Catalysis
Divalent
chemistry.chemical_compound
Colloid and Surface Chemistry
Monomer
Adenosine Triphosphate
chemistry
Sequestosome-1 Protein
biology.protein
Biophysics
alpha-Synuclein
Non-covalent interactions
Chelation
Adenosine triphosphate
Subjects
Details
- ISSN :
- 15205126
- Volume :
- 143
- Issue :
- 31
- Database :
- OpenAIRE
- Journal :
- Journal of the American Chemical Society
- Accession number :
- edsair.doi.dedup.....677e018c8cd1de999b687f82242a4c97