Histidine 73 methylation coordinates β-actin plasticity in response to key environmental factors
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.
Authors
- Pengyu Y. Ren (ORCID: https://orcid.org/0000-0002-5613-1910)
- Jean‐Philip Piquemal (ORCID: https://orcid.org/0000-0001-6615-9426)
- Hugo Wioland (ORCID: https://orcid.org/0000-0001-5254-9642)
- Brandon Walker (ORCID: https://orcid.org/0000-0002-2738-3844)
- Louis Lagardère (ORCID: https://orcid.org/0000-0002-7251-0910)
- Antoine Jégou (ORCID: https://orcid.org/0000-0003-0356-3127)
- Matthieu Chavent (ORCID: https://orcid.org/0000-0003-4524-4773)
- Adrien Schahl (ORCID: https://orcid.org/0000-0001-5839-7715)
- Maya Ballet
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université Fédérale de Toulouse Midi-Pyrénées (FR)
- Université Paris Cité (FR)
- Sorbonne Université (FR)
- Laboratoire de Chimie Théorique (FR)
- Institut de Pharmacologie et de Biologie Structurale (FR)
- Institut Jacques Monod (FR)
- Laboratoire de Microbiologie et Génétique Moléculaires (FR)
- The University of Texas at Austin (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-03-07
- DOI
- https://doi.org/10.1038/s41467-025-57458-6
- Citations
- 2
- Primary Topic
- Protein Structure and Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- European Commission
- Grand Équipement National De Calcul Intensif