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, Emil Reisler

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article number2183
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

Fingerprint

Actin Cytoskeleton
Actins
filaments
nucleotides
Oxidation
oxidation
effectors
mutagenesis
enzymes
phosphates
assembly
interactions
Actin Depolymerizing Factors
microscopy
cells
Nucleotides
Mutagenesis
Site-Directed Mutagenesis
Oxidation-Reduction
Microscopy

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Grintsevich, E. E., Ge, P., Sawaya, M. R., Yesilyurt, H. G., Terman, J. R., Zhou, Z. H., & Reisler, E. (2017). Catastrophic disassembly of actin filaments via Mical-mediated oxidation. Nature Communications, 8(1), [2183]. https://doi.org/10.1038/s41467-017-02357-8

Catastrophic disassembly of actin filaments via Mical-mediated oxidation. / Grintsevich, Elena E.; Ge, Peng; Sawaya, Michael R.; Yesilyurt, Hunkar Gizem; Terman, Jonathan R.; Zhou, Z. Hong; Reisler, Emil.

In: Nature Communications, Vol. 8, No. 1, 2183, 01.12.2017.

Research output: Contribution to journalArticle

Grintsevich, EE, Ge, P, Sawaya, MR, Yesilyurt, HG, Terman, JR, Zhou, ZH & Reisler, E 2017, 'Catastrophic disassembly of actin filaments via Mical-mediated oxidation', Nature Communications, vol. 8, no. 1, 2183. https://doi.org/10.1038/s41467-017-02357-8
Grintsevich, Elena E. ; Ge, Peng ; Sawaya, Michael R. ; Yesilyurt, Hunkar Gizem ; Terman, Jonathan R. ; Zhou, Z. Hong ; Reisler, Emil. / Catastrophic disassembly of actin filaments via Mical-mediated oxidation. In: Nature Communications. 2017 ; Vol. 8, No. 1.
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