Publication Date: Tue Dec 19 00:00: Research Org.: Argonne National Lab. Department of Chemistry and Biochemistry of California, Los Angeles, CA (United States). of Microbiology, Immunology & Molecular Genetics of Neuroscience and Pharmacology and Neuroscience Graduate Program of Texas Southwestern Medical Center, Dallas, TX (United States). Thus, in conjunction with cofilin, Mical oxidation of actin promotes F-actin disassembly independent of the nucleotide-bound state. Moreover, we find that Mical oxidation of actin allows for cofilin-mediated severing even in the presence of inorganic phosphate. Site-directed mutagenesis reveals that this interaction promotes Mox-actin instability. 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). Using near-atomic resolution cryoEM reconstruction and single filament TIRF microscopy we identify two dynamic and structural states of Mox-actin. 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. 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. Actin filament assembly and disassembly are vital for cell functions.

Mical actin ucla