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Title | Catastrophic disassembly of actin filaments via Mical-mediated oxidation. |
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Journal, issue, pages | Nat Commun, Vol. 8, Issue 1, Page 2183, Year 2017 |
Publish date | Dec 19, 2017 |
Authors | Elena E Grintsevich / Peng Ge / Michael R Sawaya / Hunkar Gizem Yesilyurt / Jonathan R Terman / Z Hong Zhou / Emil Reisler / |
PubMed 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 ...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. |
External links | Nat Commun / PubMed:29259197 / PubMed Central |
Methods | EM (helical sym.) / X-ray diffraction |
Resolution | 2.39 - 3.9 Å |
Structure data | EMDB-7007, PDB-6av9: EMDB-7008, PDB-6avb: PDB-5ubo: |
Chemicals | ChemComp-CA: ChemComp-ATP: ChemComp-MPD: ChemComp-HOH: ChemComp-ADP: |
Source |
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Keywords | CONTRACTILE PROTEIN / GELSOLIN / ACTIN / METHIONINE OXIDATION / STRUCTURAL PROTEIN / F-Actin / Mical / cytoskeleton / helix |