Catastrophic disassembly of actin filaments via Mical-mediated oxidation

被引：79

作者：

Grintsevich, Elena E. ^{[1
]}

Ge, Peng ^{[2
]}

Sawaya, Michael R. ^{[1
,3
]}

Yesilyurt, Hunkar Gizem ^{[4
,5
]}

Terman, Jonathan R. ^{[4
,5
]}

Zhou, Z. Hong ^{[2
,3
,6
]}

Reisler, Emil ^{[1
]}

机构：

[1] Univ Calif UCLA, Dept Chem & Biochem, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Calif NanoSyst Inst, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA

[4] Univ Texas Southwestern Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA

[5] Univ Texas Southwestern Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA

[6] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

CRYO-EM STRUCTURE; NEAR-ATOMIC-RESOLUTION; HELICAL FILAMENTS; ATP HYDROLYSIS; MECHANISM; PROTEIN; COMPLEX; POLYMERIZATION; RECONSTRUCTION; COFILIN;

D O I：

10.1038/s41467-017-02357-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 angstrom 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.

引用

页数：10

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