Mechanism of Phosphate Release from Actin Filaments.

ABSTRACT: After ATP-actin monomers assemble filaments, the ATP's γ-phosphate is hydrolyzed within seconds and dissociates over minutes. We used all-atom molecular dynamics simulations to sample the release of phosphate from filaments and study residues that gate release. Dissociation of phosphate from Mg²⁺ is rate limiting and associated with an energy barrier of 20 kcal/mol, consistent with experimental rates of phosphate release. Phosphate then diffuses in an internal cavity toward a gate formed by R177 suggested in prior computational studies and cryo-EM structures. The gate is closed when R177 hydrogen bonds with N111 and is open when R177 forms a salt bridge with D179. Most of the time interactions of R177 with other residues occludes the phosphate release pathway. Machine learning a

SUBMITTER: Wang Y 

PROVIDER: S-EPMC10418243 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature