Catastrophic disassembly of actin filaments via Mical-mediated oxidation

Elena E. Grintsevich, Peng Ge, Michael R. Sawaya, Hunkar Gizem Yesilyurt, Jonathan R. Terman (), Z. Hong Zhou () and Emil Reisler ()
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Elena E. Grintsevich: University of California (UCLA)
Peng Ge: UCLA
Michael R. Sawaya: University of California (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
Emil Reisler: University of California (UCLA)

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: 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.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02357-8

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DOI: 10.1038/s41467-017-02357-8

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