Backbone chemical shift assignments of human 14-3-3σ
14-3-3 proteins are a group of seven dimeric adapter proteins that exert their biological function by interacting with hundreds of phosphorylated proteins, thus influencing their sub-cellular localization, activity or stability in the cell. Due to this remarkable interaction network, 14-3-3 proteins have been associated with several pathologies and the protein–protein interactions (PPIs) established with a number of partners are now considered promising drug targets. The activity of 14-3-3 proteins is often isoform specific and to our knowledge only one out of seven isoforms, 14-3-3\(\zeta\), has been assigned. Despite the availability of the crystal structures of all seven isoforms of 14-3-3, the additional NMR assignments of 14-3-3 proteins are important for both biological mechanism studies and chemical biology approaches. Herein, we present a robust backbone assignment of 14-3-3σ, which will allow advances in the discovery of potential therapeutic compounds. This assignment is now being applied to the discovery of both inhibitors and stabilizers of 14-3-3 PPIs.
KeywordsProtein–protein interactions 14-3-3 proteins Drug discovery NMR resonance assignments
We thank MSc. Eline Sijbesma and Dr. Christian Ottmann from the Eindhoven University of Technology for kindly providing us the plasmids of both 14-3-3σ and 14-3-3σΔC17. We also thank Dr. Elian Dupré from Lille University for his help with the automatic assignments software.
The research is supported by funding from the European Union through the TASPPI project (H2020-MSCA-ITN-2015, Grant Number 675179) and by the LabEx (Laboratory of Excellence) DISTALZ (ANR, ANR-11-LABX- 009). The NMR facilities were funded by the Nord Region Council, CNRS, Institut Pasteur de Lille, the European Community (ERDF), the French Ministry of Research and the University of Lille. We acknowledge support for the NMR facilities from TGE RMN THC (CNRS, FR-3050) and FRABio (Univ. Lille, CNRS, FR-3688).
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Conflict of interest
The authors declare that they have no conflict of interest.
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