Physical confinement modulates the rate-limiting transition in the release of phosphate from actin filaments
4 affiliations
- 1Department of Chemistry, Chicago Center for Theoretical Chemistry, Institute for Biophysical Dynamics, and James Franck Institute, The University of Chicago, Chicago, IL, USA.
- 2Department of Molecular Cellular and Developmental Biology, Yale University, New Haven, CT, USA.
- 3Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
- 4Department of Cell Biology, Yale University, New Haven, CT, USA.
Abstract
The nucleotide state and rates of transitions between states regulate the dynamics of ATPases. Slow inorganic phosphate (Pi) release following ATP hydrolysis is often rate limiting and associated with key conformational changes. Actin filaments offer a unique opportunity to understand the fundamentals of Pi release because identical subunits at filament ends and the interior release Pi at markedly different rates. The molecular origin of this difference is debated, so we used extensive all-atom molecular dynamics simulations to characterize Pi release from different subunits within an actin filament. The calculated dissociation rates of Pi from ADP-Mg²⁺ in the active site correlate with experimentally measured Pi release rates and scale inversely with the numbers of water molecules in the cavity surrounding the γ-phosphate. Simulations show that egress of Pi through the protein channels, including through the N111-R177 backdoor, is not rate limiting and that subunits at the filament ends use alternative egress pathways.
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BibTeX
@article{herman2026physical,
title = {{Physical confinement modulates the rate-limiting transition in the release of phosphate from actin filaments}},
author = {Kristina M. Herman and Sahithya Sridharan Iyer and Yihang Wang and Thomas D. Pollard and Gregory A. Voth},
journal = {Science Advances},
year = {2026},
month = oct,
doi = {10.1126/sciadv.aeh7206},
url = {https://www.science.org/doi/10.1126/sciadv.aeh7206},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Physical confinement modulates the rate-limiting transition in the release of phosphate from actin filaments
AU - Kristina M. Herman
AU - Sahithya Sridharan Iyer
AU - Yihang Wang
AU - Thomas D. Pollard
AU - Gregory A. Voth
PY - 2026
DA - 2026/10/21
JO - Science Advances
DO - 10.1126/sciadv.aeh7206
UR - https://www.science.org/doi/10.1126/sciadv.aeh7206
AB - The nucleotide state and rates of transitions between states regulate the dynamics of ATPases. Slow inorganic phosphate (Pi) release following ATP hydrolysis is often rate limiting and associated with key conformational changes. Actin filaments offer a unique opportunity to understand the fundamentals of Pi release because identical subunits at filament ends and the interior release Pi at markedly different rates. The molecular origin of this difference is debated, so we used extensive all-atom molecular dynamics simulations to characterize Pi release from different subunits within an actin filament. The calculated dissociation rates of Pi from ADP-Mg²⁺ in the active site correlate with experimentally measured Pi release rates and scale inversely with the numbers of water molecules in the cavity surrounding the γ-phosphate. Simulations show that egress of Pi through the protein channels, including through the N111-R177 backdoor, is not rate limiting and that subunits at the filament ends use alternative egress pathways.
SN - 2375-2548
ER -