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Microtubules accelerate the kinase activity of Aurora-B by a reduction in dimensionality.

Publication ,  Journal Article
Noujaim, M; Bechstedt, S; Wieczorek, M; Brouhard, GJ
Published in: Plos One
January 2014

Aurora-B is the kinase subunit of the Chromosome Passenger Complex (CPC), a key regulator of mitotic progression that corrects improper kinetochore attachments and establishes the spindle midzone. Recent work has demonstrated that the CPC is a microtubule-associated protein complex and that microtubules are able to activate the CPC by contributing to Aurora-B auto-phosphorylation in trans. Aurora-B activation is thought to occur when the local concentration of Aurora-B is high, as occurs when Aurora-B is enriched at centromeres. It is not clear, however, whether distributed binding to large structures such as microtubules would increase the local concentration of Aurora-B. Here we show that microtubules accelerate the kinase activity of Aurora-B by a "reduction in dimensionality." We find that microtubules increase the kinase activity of Aurora-B toward microtubule-associated substrates while reducing the phosphorylation levels of substrates not associated to microtubules. Using the single molecule assay for microtubule-associated proteins, we show that a minimal CPC construct binds to microtubules and diffuses in a one-dimensional (1D) random walk. The binding of Aurora-B to microtubules is salt-dependent and requires the C-terminal tails of tubulin, indicating that the interaction is electrostatic. We show that the rate of Aurora-B auto-activation is faster with increasing concentrations of microtubules. Finally, we demonstrate that microtubules lose their ability to stimulate Aurora-B when their C-terminal tails are removed by proteolysis. We propose a model in which microtubules act as scaffolds for the enzymatic activity of Aurora-B. The scaffolding activity of microtubules enables rapid Aurora-B activation and efficient phosphorylation of microtubule-associated substrates.

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Published In

Plos One

DOI

EISSN

1932-6203

ISSN

1932-6203

Publication Date

January 2014

Volume

9

Issue

2

Start / End Page

e86786

Related Subject Headings

  • Xenopus laevis
  • Xenopus Proteins
  • Substrate Specificity
  • Protein Structure, Tertiary
  • Protein Binding
  • Phosphorylation
  • Models, Molecular
  • Models, Biological
  • Microtubules
  • Kinetics
 

Citation

APA
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ICMJE
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Noujaim, M., Bechstedt, S., Wieczorek, M., & Brouhard, G. J. (2014). Microtubules accelerate the kinase activity of Aurora-B by a reduction in dimensionality. Plos One, 9(2), e86786. https://doi.org/10.1371/journal.pone.0086786
Noujaim, Michael, Susanne Bechstedt, Michal Wieczorek, and Gary J. Brouhard. “Microtubules accelerate the kinase activity of Aurora-B by a reduction in dimensionality.Plos One 9, no. 2 (January 2014): e86786. https://doi.org/10.1371/journal.pone.0086786.
Noujaim M, Bechstedt S, Wieczorek M, Brouhard GJ. Microtubules accelerate the kinase activity of Aurora-B by a reduction in dimensionality. Plos One. 2014 Jan;9(2):e86786.
Noujaim, Michael, et al. “Microtubules accelerate the kinase activity of Aurora-B by a reduction in dimensionality.Plos One, vol. 9, no. 2, Jan. 2014, p. e86786. Epmc, doi:10.1371/journal.pone.0086786.
Noujaim M, Bechstedt S, Wieczorek M, Brouhard GJ. Microtubules accelerate the kinase activity of Aurora-B by a reduction in dimensionality. Plos One. 2014 Jan;9(2):e86786.

Published In

Plos One

DOI

EISSN

1932-6203

ISSN

1932-6203

Publication Date

January 2014

Volume

9

Issue

2

Start / End Page

e86786

Related Subject Headings

  • Xenopus laevis
  • Xenopus Proteins
  • Substrate Specificity
  • Protein Structure, Tertiary
  • Protein Binding
  • Phosphorylation
  • Models, Molecular
  • Models, Biological
  • Microtubules
  • Kinetics