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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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    1. Alex W. Wilkinson & Jonathan Diep & Shaobo Dai & Shuo Liu & Yaw Shin Ooi & Dan Song & Tie-Mei Li & John R. Horton & Xing Zhang & Chao Liu & Darshan V. Trivedi & Katherine M. Ruppel & José G. Vilches-M, 2019. "SETD3 is an actin histidine methyltransferase that prevents primary dystocia," Nature, Nature, vol. 565(7739), pages 372-376, January.
    2. Matthew J. Reynolds & Carla Hachicho & Ayala G. Carl & Rui Gong & Gregory M. Alushin, 2022. "Bending forces and nucleotide state jointly regulate F-actin structure," Nature, Nature, vol. 611(7935), pages 380-386, November.
    3. Peter Nietmann & Kevin Kaub & Andrejus Suchenko & Susanne Stenz & Claas Warnecke & Mohan K. Balasubramanian & Andreas Janshoff, 2023. "Cytosolic actin isoforms form networks with different rheological properties that indicate specific biological function," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
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