Catalysis of the microtubule on-rate is the major parameter regulating the depolymerase activity of MCAK
Open Access
- 6 December 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Structural & Molecular Biology
- Vol. 17 (1), 77-82
- https://doi.org/10.1038/nsmb.1728
Abstract
MCAK is a mitotic kinesin that binds to and slides along microtubules (MT) to reach their ends, where MCAK disassembles MTs into tubulin dimers. Now the kinetics of MCAK-MT interaction are directly observed in a single-molecule setup, dissecting the contributions of different MCAK regions to on-rates and tubulin disassembly activity. The kinesin-13, MCAK, is a critical regulator of microtubule dynamics in eukaryotic cells. We have functionally dissected the structural features responsible for MCAK's potent microtubule depolymerization activity. MCAK's positively charged neck enhances its delivery to microtubule ends not by tethering the molecule to microtubules during diffusion, as commonly thought, but by catalyzing the association of MCAK to microtubules. On the other hand, this same positively charged neck slightly diminishes MCAK's ability to remove tubulin subunits once at the microtubule end. Conversely, dimerization reduces MCAK delivery but improves MCAK's ability to remove tubulin subunits. The reported kinetics for these events predicts a nonspecific binding mechanism that may represent a paradigm for the diffusive interaction of many microtubule-binding proteins.Keywords
This publication has 32 references indexed in Scilit:
- An EB1-Binding Motif Acts as a Microtubule Tip Localization SignalCell, 2009
- The Ndc80 Kinetochore Complex Forms Load-Bearing Attachments to Dynamic Microtubule Tips via Biased DiffusionCell, 2009
- The diffusive interaction of microtubule binding proteinsCurrent Opinion in Cell Biology, 2009
- CENP-E combines a slow, processive motor and a flexible coiled coil to produce an essential motile kinetochore tetherThe Journal of cell biology, 2008
- Phosphoregulation and depolymerization-driven movement of the Dam1 complex do not require ring formationNature, 2008
- MCAK facilitates chromosome movement by promoting kinetochore microtubule turnoverThe Journal of cell biology, 2007
- Myosin Va maneuvers through actin intersections and diffuses along microtubulesProceedings of the National Academy of Sciences of the United States of America, 2007
- What Drives Proteins into the Major or Minor Grooves of DNA?Journal of Molecular Biology, 2007
- The bipolar mitotic kinesin Eg5 moves on both microtubules that it crosslinksNature, 2005
- Ordered water structure around a B-DNA dodecamer: A quantitative studyJournal of Molecular Biology, 1983