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

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....

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Bibliographic Details
Main Authors: Adrien Schahl, Louis Lagardère, Brandon Walker, Pengyu Ren, Hugo Wioland, Maya Ballet, Antoine Jégou, Matthieu Chavent, Jean-Philip Piquemal
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-57458-6
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Summary: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.
ISSN:2041-1723