Frontiers in Molecular Biosciences (Dec 2021)

Cellular ATP Levels Determine the Stability of a Nucleotide Kinase

  • Oliver Brylski,
  • Oliver Brylski,
  • Oliver Brylski,
  • Puja Shrestha,
  • Puja Shrestha,
  • Patricia Gnutt,
  • David Gnutt,
  • David Gnutt,
  • David Gnutt,
  • Jonathan Wolf Mueller,
  • Jonathan Wolf Mueller,
  • Simon Ebbinghaus,
  • Simon Ebbinghaus,
  • Simon Ebbinghaus

DOI
https://doi.org/10.3389/fmolb.2021.790304
Journal volume & issue
Vol. 8

Abstract

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The energy currency of the cell ATP, is used by kinases to drive key cellular processes. However, the connection of cellular ATP abundance and protein stability is still under investigation. Using Fast Relaxation Imaging paired with alanine scanning and ATP depletion experiments, we study the nucleotide kinase (APSK) domain of 3′-phosphoadenosine-5′-phosphosulfate (PAPS) synthase, a marginally stable protein. Here, we show that the in-cell stability of the APSK is determined by ligand binding and directly connected to cellular ATP levels. The observed protein stability change for different ligand-bound states or under ATP-depleted conditions ranges from ΔGf0 = -10.7 to +13.8 kJ/mol, which is remarkable since it exceeds changes measured previously, for example upon osmotic pressure, cellular stress or differentiation. The results have implications for protein stability during the catalytic cycle of APS kinase and suggest that the cellular ATP level functions as a global regulator of kinase activity.

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