The release of inorganic phosphate (Pi) from actin marks old actin filaments for disassembly. By combining cryo-electron microscopy (cryo-EM) with in vitro reconstitution and molecular dynamics simulations, we show how actin filaments release Pi through a ‘molecular backdoor’ and demonstrate that this arrangement is distorted in a disease-linked actin variant.
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References
Merino, F., Pospich, S. & Raunser, S. Towards a structural understanding of the remodeling of the actin cytoskeleton. Semin. Cell Dev. Biol. 102, 51–64 (2020). A review article that describes the fundamental functions of actin filaments in cells and how they are regulated by ABPs.
Oosterheert, W. et al. Structural basis of actin filament assembly and aging. Nature 611, 374–379 (2022). This paper, which motivated our Pi release study, reveals high resolution structural insights into the assembly and aging of actin filaments.
Carlier, M. F. & Pantaloni, D. Direct evidence for ADP–Pi–F-actin as the major intermediate in ATP–actin polymerization. Rate of dissociation of Pi from actin filaments. Biochemistry 25, 7789–7792 (1986). This pioneering study provides evidence that ADP-Pi-bound F-actin represents a distinct, metastable state of the filament.
Jégou, A. et al. Individual actin filaments in a microfluidic flow reveal the mechanism of ATP hydrolysis and give insight into the properties of profilin. PLoS Biol. 9, e1001161 (2011). This paper provides conclusive evidence that Pi release from F-actin is a stochastic process and shows that Pi escapes much faster from actin subunits at the barbed end than from those at the filament core.
Lappalainen, P., Kotila, T., Jégou, A. & Romet-Lemonne, G. Biochemical and mechanical regulation of actin dynamics. Nat. Rev. Mol. Cell Biol. 23, 836–852 (2022). A recent review article that discusses how actin filament turnover is regulated in dynamic cellular actin networks.
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This is a summary of: Oosterheert, W. et al. Molecular mechanisms of inorganic-phosphate release from the core and barbed end of actin filaments. Nat. Struct. Mol. Biol. https://doi.org/10.1038/s41594-023-01101-9 (2023).
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The great escape — how inorganic phosphate is released from actin filaments. Nat Struct Mol Biol 30, 1621–1622 (2023). https://doi.org/10.1038/s41594-023-01102-8
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DOI: https://doi.org/10.1038/s41594-023-01102-8
