Format

Send to

Choose Destination
Dev Cell. 2017 Jul 10;42(1):37-51.e8. doi: 10.1016/j.devcel.2017.06.011.

A Tubulin Binding Switch Underlies Kip3/Kinesin-8 Depolymerase Activity.

Author information

1
Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02215, USA.
2
Department of Biophysics, UT Southwestern, Dallas, TX 75390, USA.
3
Department of Biomedical Engineering, Penn State University, University Park, PA 16802, USA.
4
Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94143, USA.
5
Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02215, USA. Electronic address: david_pellman@dfci.harvard.edu.

Abstract

Kinesin-8 motors regulate the size of microtubule structures, using length-dependent accumulation at the plus end to preferentially disassemble long microtubules. Despite extensive study, the kinesin-8 depolymerase mechanism remains under debate. Here, we provide evidence for an alternative, tubulin curvature-sensing model of microtubule depolymerization by the budding yeast kinesin-8, Kip3. Kinesin-8/Kip3 uses ATP hydrolysis, like other kinesins, for stepping on the microtubule lattice, but at the plus end Kip3 undergoes a switch: its ATPase activity is suppressed when it binds tightly to the curved conformation of tubulin. This prolongs plus-end binding, stabilizes protofilament curvature, and ultimately promotes microtubule disassembly. The tubulin curvature-sensing model is supported by our identification of Kip3 structural elements necessary and sufficient for plus-end binding and depolymerase activity, as well as by the identification of an α-tubulin residue specifically required for the Kip3-curved tubulin interaction. Together, these findings elucidate a major regulatory mechanism controlling the size of cellular microtubule structures.

KEYWORDS:

depolymerization; kinesins; microtubule associated proteins; microtubule dynamics; spindle scaling

PMID:
28697331
PMCID:
PMC5573156
DOI:
10.1016/j.devcel.2017.06.011
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center