5UBO

Mical-oxidized Actin complex with Gelsolin Segment 1

Summary for 5UBO

• Entry DOI: 10.2210/pdb5ubo/pdb
• Related: 1EQY
• Descriptor: Actin, alpha skeletal muscle, Gelsolin, CALCIUM ION, ... (6 entities in total)
• Functional Keywords: gelsolin, actin, contractile protein, methionine oxidation
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 57213.70

Authors

Grintsevich, E.E.,Sawaya, M.R.,Reisler, E. (deposition date: 2016-12-21, release date: 2017-12-20, Last modification date: 2023-10-04)

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

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: 29259197
DOI: 10.1038/s41467-017-02357-8

Experimental method

X-RAY DIFFRACTION (2.39 Å)