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Structure paper

TitleCatastrophic disassembly of actin filaments via Mical-mediated oxidation.
Journal, issue, pagesNat Commun, Vol. 8, Issue 1, Page 2183, Year 2017
Publish dateDec 19, 2017
AuthorsElena E Grintsevich / Peng Ge / Michael R Sawaya / Hunkar Gizem Yesilyurt / Jonathan R Terman / Z Hong Zhou / Emil Reisler /
PubMed AbstractActin 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.
External linksNat Commun / PubMed:29259197 / PubMed Central
MethodsEM (helical sym.) / X-ray diffraction
Resolution2.39 - 3.9 Å
Structure data

7007

6av9

EMDB-7007, PDB-6av9:
CryoEM structure of Mical Oxidized Actin (Class 1)
Method: EM (helical sym.) / Resolution: 3.9 Å

7008

6avb

EMDB-7008, PDB-6avb:
CryoEM structure of Mical Oxidized Actin (Class 1)
Method: EM (helical sym.) / Resolution: 3.9 Å

PDB-5ubo:
Mical-oxidized Actin complex with Gelsolin Segment 1
Method: X-RAY DIFFRACTION / Resolution: 2.39 Å

Chemicals

ChemComp-CA:
Unknown entry

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM / Adenosine triphosphate

ChemComp-MPD:
(4S)-2-METHYL-2,4-PENTANEDIOL / precipitant*YM / 2-Methyl-2,4-pentanediol

ChemComp-HOH:
WATER / Water

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM / Adenosine diphosphate

Source
  • oryctolagus cuniculus (rabbit)
  • Rabbit (rabbit)
  • homo sapiens (human)
KeywordsCONTRACTILE PROTEIN / GELSOLIN / ACTIN / METHIONINE OXIDATION / STRUCTURAL PROTEIN / F-Actin / Mical / cytoskeleton / helix

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