Atherton, Joseph and Yu, I-M. and Cook, Alexander and Muretta, J. and Joseph, Agnel Praveen and Major, J. and Sourigues, Y. and Clause, J. and Topf, Maya and Rosenfeld, S. and Houdusse, A. and Moores, Carolyn A. (2017) The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry. eLife , ISSN 2050-084X.
|
Text
13-04-2017-RA-eLife-27793R1_Merged_PDF.pdf - Published Version of Record Available under License Creative Commons Attribution. Download (109MB) | Preview |
Abstract
MKLP2, a kinesin-6, has critical roles during the metaphase-anaphase transition and cytokinesis. Its motor domain contains conserved nucleotide binding motifs, but is divergent in sequence (~35% identity) and size (~40% larger) compared to other kinesins. Using cryo-electron microscopy and biophysical assays, we have undertaken a mechanochemical dissection of the microtubule-bound MKLP2 motor domain during its ATPase cycle, and show that many facets of its mechanism are distinct from other kinesins. While the MKLP2 neck-linker is directed towards the microtubule plus-end in an ATP-like state, it does not fully dock along the motor domain. Furthermore, the footprint of the MKLP2 motor domain on the MT surface is altered compared to motile kinesins, and enhanced by kinesin-6-specific sequences. The conformation of the highly extended loop6 insertion characteristic of kinesin-6s is nucleotide-independent and does not contact the MT surface. Our results emphasize the role of family-specific insertions in modulating kinesin motor function.
Metadata
| Item Type: | Article |
|---|---|
| Keyword(s) / Subject(s): | cryo-EM, microtubules, kinesin, structural biology, mitosis |
| School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Depositing User: | Carolyn Moores |
| Date Deposited: | 15 Aug 2017 07:40 |
| Last Modified: | 02 Aug 2023 17:34 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/19333 |
Statistics
Additional statistics are available via IRStats2.
Archive Staff Only (login required)
