Engineered kinesin motor proteins amenable to small-molecule inhibition

Martin F. Engelke, Michael Winding, Yang Yue, Shankar Shastry, Federico Teloni, Sanjay Reddy, T. Lynne Blasius, Pushpanjali Soppina, William O. Hancock, Vladimir I. Gelfand, Kristen J. Verhey

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The human genome encodes 45 kinesin motor proteins that drive cell division, cell motility, intracellular trafficking and ciliary function. Determining the cellular function of each kinesin would benefit from specific small-molecule inhibitors. However, screens have yielded only a few specific inhibitors. Here we present a novel chemical-genetic approach to engineer kinesin motors that can carry out the function of the wild-type motor yet can also be efficiently inhibited by small, cell-permeable molecules. Using kinesin-1 as a prototype, we develop two independent strategies to generate inhibitable motors, and characterize the resulting inhibition in single-molecule assays and in cells. We further apply these two strategies to create analogously inhibitable kinesin-3 motors. These inhibitable motors will be of great utility to study the functions of specific kinesins in a dynamic manner in cells and animals. Furthermore, these strategies can be used to generate inhibitable versions of any motor protein of interest.

Original languageEnglish (US)
Article number11159
JournalNature communications
Volume7
DOIs
StatePublished - Apr 5 2016

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Kinesin
proteins
Molecules
molecules
Proteins
cells
inhibitors
cell division
Human Genome
locomotion
genome
Cell Division
Cell Movement
engineers
animals
Assays
Animals
Genes
prototypes
Cells

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Engelke, M. F., Winding, M., Yue, Y., Shastry, S., Teloni, F., Reddy, S., ... Verhey, K. J. (2016). Engineered kinesin motor proteins amenable to small-molecule inhibition. Nature communications, 7, [11159]. https://doi.org/10.1038/ncomms11159
Engelke, Martin F. ; Winding, Michael ; Yue, Yang ; Shastry, Shankar ; Teloni, Federico ; Reddy, Sanjay ; Blasius, T. Lynne ; Soppina, Pushpanjali ; Hancock, William O. ; Gelfand, Vladimir I. ; Verhey, Kristen J. / Engineered kinesin motor proteins amenable to small-molecule inhibition. In: Nature communications. 2016 ; Vol. 7.
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Engelke, MF, Winding, M, Yue, Y, Shastry, S, Teloni, F, Reddy, S, Blasius, TL, Soppina, P, Hancock, WO, Gelfand, VI & Verhey, KJ 2016, 'Engineered kinesin motor proteins amenable to small-molecule inhibition', Nature communications, vol. 7, 11159. https://doi.org/10.1038/ncomms11159

Engineered kinesin motor proteins amenable to small-molecule inhibition. / Engelke, Martin F.; Winding, Michael; Yue, Yang; Shastry, Shankar; Teloni, Federico; Reddy, Sanjay; Blasius, T. Lynne; Soppina, Pushpanjali; Hancock, William O.; Gelfand, Vladimir I.; Verhey, Kristen J.

In: Nature communications, Vol. 7, 11159, 05.04.2016.

Research output: Contribution to journalArticle

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AU - Reddy, Sanjay

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Engelke MF, Winding M, Yue Y, Shastry S, Teloni F, Reddy S et al. Engineered kinesin motor proteins amenable to small-molecule inhibition. Nature communications. 2016 Apr 5;7. 11159. https://doi.org/10.1038/ncomms11159