The structural basis of the multi-step allosteric activation of Aurora B kinase
Abstract
Aurora B, together with IN-box, the C-terminal part of INCENP, forms an enzymatic complex that ensures faithful cell division. The [Aurora B/IN-box] complex is activated by autophosphorylation in the Aurora B activation loop and in IN-box, but it is not clear how these phosphorylations activate the enzyme. We used a combination of experimental and computational studies to investigate the effects of phosphorylation on the molecular dynamics and structure of [Aurora B/IN-box]. In addition, we generated partially phosphorylated intermediates to analyze the contribution of each phosphorylation independently. We found that the dynamics of Aurora and IN-box are interconnected, and IN-box plays both positive and negative regulatory roles depending on the phosphorylation status of the enzyme complex. Phosphorylation in the activation loop of Aurora B occurs intramolecularly and prepares the enzyme complex for activation, but two phosphorylated sites are synergistically responsible for full enzyme activity.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. The mass spectrometry proteomics data are available through the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD038935.
Article and author information
Author details
Funding
Norges Forskningsråd (187615)
- Dario Segura-Peña
- Oda Hovet
- Hemanga Gogoi
- Stine Malene Hansen Wøien
- Nikolina Sekulic
Norges Forskningsråd (262695)
- Oda Hovet
- Manuel Carrer
- Michele Cascella
Norwegian Supercomputing Program (NN4654K)
- Oda Hovet
- Manuel Carrer
- Michele Cascella
Norges Forskningsråd (325528)
- Nikolina Sekulic
National Institute of General Medical Sciences (R35-GM130302)
- Jennine Dawicki-McKenna
- Ben E Black
National Institute of General Medical Sciences (GM108360)
- Jennine Dawicki-McKenna
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Sierra Cullati, Vanderbilt University, United States
Version history
- Preprint posted: November 24, 2022 (view preprint)
- Received: December 2, 2022
- Accepted: May 20, 2023
- Accepted Manuscript published: May 25, 2023 (version 1)
- Version of Record published: June 7, 2023 (version 2)
Copyright
© 2023, Segura-Peña et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Further reading
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