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Nat Struct Mol Biol. 2018 Jun;25(6):528-537. doi: 10.1038/s41594-018-0074-0. Epub 2018 Jun 4.

Structural transitions of F-actin upon ATP hydrolysis at near-atomic resolution revealed by cryo-EM.

Author information

1
Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
2
Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
3
Institute of Organic and Macromolecular Chemistry, Friedrich-Schiller-Universität Jena, Jena, Germany.
4
Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany. stefan.raunser@mpi-dortmund.mpg.de.

Abstract

The function of actin is coupled to the nucleotide bound to its active site. ATP hydrolysis is activated during polymerization; a delay between hydrolysis and inorganic phosphate (Pi) release results in a gradient of ATP, ADP-Pi and ADP along actin filaments (F-actin). Actin-binding proteins can recognize F-actin's nucleotide state, using it as a local 'age' tag. The underlying mechanism is complex and poorly understood. Here we report six high-resolution cryo-EM structures of F-actin from rabbit skeletal muscle in different nucleotide states. The structures reveal that actin polymerization repositions the proposed catalytic base, His161, closer to the γ-phosphate. Nucleotide hydrolysis and Pi release modulate the conformational ensemble at the periphery of the filament, thus resulting in open and closed states, which can be sensed by coronin-1B. The drug-like toxin jasplakinolide locks F-actin in an open state. Our results demonstrate in detail how ATP hydrolysis links to F-actin's conformational dynamics and protein interaction.

PMID:
29867215
DOI:
10.1038/s41594-018-0074-0

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