Journal article
The crystal structure and biochemical characterization of Kif15: a bifunctional molecular motor involved in bipolar spindle formation and neuronal development
Acta crystallographica. Section D, Biological crystallography., v 70(Pt 1)
Jan 2014
PMID: 24419385
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Kinesins constitute a superfamily of microtubule-based motor proteins with important cellular functions ranging from intracellular transport to cell division. Some kinesin family members function during the mitotic phase of the eukaryotic cell cycle and are crucial for the successful progression of cell division. In the early stages of mitosis, during prometaphase, certain kinesins are required for the formation of the bipolar spindle, such as Eg5 and Kif15, which seem to possess partially overlapping functions. Because kinesins transform the chemical energy from ATP hydrolysis into mechanical work, inhibition of their function is a tractable approach for drug development. Drugs targeting Eg5 have shown promise as anticancer agents. Kif15 has recently come to the fore because it can substitute the functions of Eg5, and may itself have potential as a prospective drug target. Here, the initial biochemical, kinetic and structural characterization of Kif15 is reported and it is compared with the functionally related motor Eg5. Although Kif15 contains ADP in the catalytic site, its motor-domain structure was captured in the `ATP-like' configuration, with the neck linker docked to the catalytic core. The interaction of Kif15 with microtubules was also investigated and structural differences between these two motors were elucidated which indicate profound differences in their mode of action, in agreement with current models of microtubule cross-linking and sliding.
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Details
- Title
- The crystal structure and biochemical characterization of Kif15: a bifunctional molecular motor involved in bipolar spindle formation and neuronal development
- Creators
- Marta Klejnot - The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, ScotlandAditi Falnikar - Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USAVenkatasubramanian Ulaganathan - The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, ScotlandRobert A Cross - Warwick Medical School, University of Warwick, Coventry CV4 7AL, EnglandPeter W Baas - Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USAFrank Kozielski - School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, England
- Publication Details
- Acta crystallographica. Section D, Biological crystallography., v 70(Pt 1)
- Publisher
- Intl Union of Crystallography; United States
- Grant note
- Cancer Research UK R01 NS028785 / NINDS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000329942900014
- Scopus ID
- 2-s2.0-84892416734
- Other Identifier
- 991014878147704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemical Research Methods
- Biochemistry & Molecular Biology
- Biophysics
- Crystallography