6AVB
CryoEM structure of Mical Oxidized Actin (Class 1)
Summary for 6AVB
| Entry DOI | 10.2210/pdb6avb/pdb |
| Related | 5AV9 |
| EMDB information | 7007 7008 |
| Descriptor | Actin, alpha skeletal muscle, ADENOSINE-5'-DIPHOSPHATE (2 entities in total) |
| Functional Keywords | f-actin, mical, cytoskeleton, helix, structural protein |
| Biological source | Oryctolagus cuniculus (Rabbit) |
| Total number of polymer chains | 3 |
| Total formula weight | 127707.52 |
| Authors | Grintsevich, E.E.,Ge, P.,Sawaya, M.R.,Yesilyurt, H.G.,Terman, J.R.,Zhou, Z.H.,Reisler, E. (deposition date: 2017-09-01, release date: 2018-01-17, Last modification date: 2019-11-06) |
| Primary citation | Grintsevich, E.E.,Ge, P.,Sawaya, M.R.,Yesilyurt, H.G.,Terman, J.R.,Zhou, Z.H.,Reisler, E. Catastrophic disassembly of actin filaments via Mical-mediated oxidation. Nat Commun, 8:2183-2183, 2017 Cited by 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 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. PubMed: 29259197DOI: 10.1038/s41467-017-02357-8 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.9 Å) |
Structure validation
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