Bayliss, R orcid.org/0000-0003-0604-2773, Burgess, SG and McIntyre, PJ (2017) Switching Aurora-A kinase on and off at an allosteric site. The FEBS Journal, 284 (18). pp. 2947-2954. ISSN 1742-464X
Abstract
Protein kinases are central players in the regulation of cell cycle and signalling pathways. Their catalytic activities are strictly regulated through post-translational modifications and protein–protein interactions that control switching between inactive and active states. These states have been studied extensively using protein crystallography, although the dynamic nature of protein kinases makes it difficult to capture all relevant states. Here, we describe two recent structures of Aurora-A kinase that trap its active and inactive states. In both cases, Aurora-A is trapped through interaction with a synthetic protein, either a single-domain antibody that inhibits the kinase or a hydrocarbon-stapled peptide that activates the kinase. These structures show how the distinct synthetic proteins target the same allosteric pocket with opposing effects on activity. These studies pave the way for the development of tools to probe these allosteric mechanisms in cells.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2017, Federation of European Biochemical Societies. This is the peer reviewed version of the following article: 'Bayliss, R , Burgess, SG and McIntyre, PJ (2017) Switching Aurora-A kinase on and off at an allosteric site. The FEBS Journal, 284 (18). pp. 2947-2954,' which has been published in final form at [https://doi.org/10.1111/febs.14069]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. |
Keywords: | allostery; kinase inhibitor; protein kinase; protein-protein interaction |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > University of Leeds Research Centres and Institutes > Astbury Centre for Structural Molecular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 20 Apr 2017 14:42 |
Last Modified: | 26 Mar 2018 00:38 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1111/febs.14069 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:115219 |