National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM071940
米国
National Science Foundation (NSF, United States)
DMR-1548924
米国
引用
ジャーナル: Nat Commun / 年: 2017 タイトル: Catastrophic disassembly of actin filaments via Mical-mediated oxidation. 著者: Elena E Grintsevich / Peng Ge / Michael R Sawaya / Hunkar Gizem Yesilyurt / Jonathan R Terman / Z Hong Zhou / Emil Reisler / 要旨: 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.