6av9

Publication Abstract from PubMed

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 A 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.

Catastrophic disassembly of actin filaments via Mical-mediated oxidation.,Grintsevich EE, Ge P, Sawaya MR, Yesilyurt HG, Terman JR, Zhou ZH, Reisler E Nat Commun. 2017 Dec 19;8(1):2183. doi: 10.1038/s41467-017-02357-8. PMID:29259197^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.