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Histidine 73 methylation coordinates β-actin plasticity in response to key environmental factors

Author

Listed:
  • Adrien Schahl

    (Université de Toulouse, CNRS
    Sorbonne Université, UMR 7616 CNRS)

  • Louis Lagardère

    (Sorbonne Université, UMR 7616 CNRS)

  • Brandon Walker

    (The University of Texas at Austin)

  • Pengyu Ren

    (The University of Texas at Austin)

  • Hugo Wioland

    (Université Paris Cité, CNRS)

  • Maya Ballet

    (Université Paris Cité, CNRS)

  • Antoine Jégou

    (Université Paris Cité, CNRS)

  • Matthieu Chavent

    (Université de Toulouse, CNRS
    Université de Toulouse, CNRS)

  • Jean-Philip Piquemal

    (Sorbonne Université, UMR 7616 CNRS)

Abstract

The functional importance of the methylation of histidine 73 (H73) in actin remains unclear. Focusing on cytoplasmic β-actin, present in all mammalian cells, we use molecular dynamics simulations with a polarizable force field and adaptive sampling to examine the effects of H73 methylation. Our results show that methylation enhances nucleotide binding cleft opening, alters allosteric pathways connecting subdomains 2 and 4 (SD2 and SD4) in G-actin, and affects backdoor openings and inorganic phosphate release in F-actin, as validated by biochemical assays. These effects depend on the nucleotide and ions interacting with the actin. Together, our findings reveal how H73 methylation regulates β-actin plasticity and integrates environmental cues.

Suggested Citation

  • Adrien Schahl & Louis Lagardère & Brandon Walker & Pengyu Ren & Hugo Wioland & Maya Ballet & Antoine Jégou & Matthieu Chavent & Jean-Philip Piquemal, 2025. "Histidine 73 methylation coordinates β-actin plasticity in response to key environmental factors," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57458-6
    DOI: 10.1038/s41467-025-57458-6
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