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J Biol Chem. 2013 Jul 5;288(27):19785-95. doi: 10.1074/jbc.M113.463695. Epub 2013 May 17.

Binding of the CYK-4 subunit of the centralspindlin complex induces a large scale conformational change in the kinesin subunit.

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Departments of Molecular Genetics and Cell Biology, University of Chicago, Chicago, Illinois 60637, USA.


Centralspindlin is a critical regulator of cytokinesis in animal cells. It is a tetramer consisting of ZEN-4/MKLP1, a kinesin-6 motor, and CYK-4/MgcRacGAP, a Rho GTPase-activating protein. At anaphase, centralspindlin localizes to a narrow region of antiparallel microtubule overlap and initiates central spindle assembly. Central spindle assembly requires complex formation between ZEN-4 and CYK-4. However, the structural consequences of CYK-4 binding to ZEN-4 are unclear as are the mechanisms of microtubule bundling. Here we investigate whether CYK-4 binding induces a conformational change in ZEN-4. Characterization of the structure and conformational dynamics of the minimal interacting regions between ZEN-4 and CYK-4 by continuous wave EPR and double electron-electron resonance (DEER) spectroscopy reveals that CYK-4 binding dramatically stabilizes the relative positions of the neck linker regions of ZEN-4. Additionally, our data indicate that each neck linker is similarly structured in the bound and unbound states. CYK-4 binding decreases the rate of ZEN-4-mediated microtubule gliding. These results constrain models for the molecular organization of centralspindlin.


Cytokinesis; Electron Paramagnetic Resonance (EPR); Kinesin; Microtubules; Molecular Motors

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