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Catastrophic disassembly of actin filaments via Mical-mediated oxidation

Author

Listed:
  • Elena E. Grintsevich

    (University of California (UCLA))

  • Peng Ge

    (UCLA)

  • Michael R. Sawaya

    (University of California (UCLA)
    UCLA)

  • Hunkar Gizem Yesilyurt

    (The University of Texas Southwestern Medical Center)

  • Jonathan R. Terman

    (The University of Texas Southwestern Medical Center)

  • Z. Hong Zhou

    (UCLA
    UCLA
    Immunology & Molecular Genetics, UCLA)

  • Emil Reisler

    (University of California (UCLA)
    UCLA)

Abstract

Actin filament assembly and disassembly are vital for cell functions. MICAL Redox enzymes are important post-translational effectors of actin that stereo-specifically oxidize actin’s M44 and M47 residues to induce cellular F-actin disassembly. Here we show that Mical-oxidized (Mox) actin can undergo extremely fast (84 subunits/s) disassembly, which depends on F-actin’s nucleotide-bound state. Using near-atomic resolution cryoEM reconstruction and single filament TIRF microscopy we identify two dynamic and structural states of Mox-actin. Modeling actin’s D-loop region based on our 3.9 Å cryoEM reconstruction suggests that oxidation by Mical reorients the side chain of M44 and induces a new intermolecular interaction of actin residue M47 (M47-O-T351). Site-directed mutagenesis reveals that this interaction promotes Mox-actin instability. Moreover, we find that Mical oxidation of actin allows for cofilin-mediated severing even in the presence of inorganic phosphate. Thus, in conjunction with cofilin, Mical oxidation of actin promotes F-actin disassembly independent of the nucleotide-bound state.

Suggested Citation

  • Elena E. Grintsevich & Peng Ge & Michael R. Sawaya & Hunkar Gizem Yesilyurt & Jonathan R. Terman & Z. Hong Zhou & Emil Reisler, 2017. "Catastrophic disassembly of actin filaments via Mical-mediated oxidation," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02357-8
    DOI: 10.1038/s41467-017-02357-8
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