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Biomolecular NMR Assignments

, Volume 13, Issue 1, pp 103–107 | Cite as

Backbone chemical shift assignments of human 14-3-3σ

  • João Filipe Neves
  • Isabelle LandrieuEmail author
  • Hamida Merzougui
  • Emmanuelle Boll
  • Xavier Hanoulle
  • François-Xavier Cantrelle
Article

Abstract

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.

Keywords

Protein–protein interactions 14-3-3 proteins Drug discovery NMR resonance assignments 

Notes

Acknowledgements

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.

Funding

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).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Andrei SA, Meijer FA, Neves JF et al (2018) Inhibition of 14-3-3/tau by hybrid small-molecule peptides operating via two different binding modes. ACS Chem Neurosci.  https://doi.org/10.1021/acschemneuro.8b00118 Google Scholar
  2. Bahrami A, Assadi AH, Markley JL, Eghbalnia HR (2009) Probabilistic interaction network of evidence algorithm and its application to complete labeling of peak lists from protein NMR spectroscopy. PLoS Comput Biol 5:e1000307.  https://doi.org/10.1371/journal.pcbi.1000307 ADSCrossRefGoogle Scholar
  3. Fu H, Subramanian RR, Masters SC (2000) 14-3-3 proteins: structure, function, and regulation. Annu Rev Pharmacol Toxicol 40:617–647CrossRefGoogle Scholar
  4. Hafsa NE, Arndt D, Wishart DS (2015) CSI 3.0: a web server for identifying secondary and super-secondary structure in proteins using NMR chemical shifts. Nucleic Acids Res 43:W370–W377.  https://doi.org/10.1093/nar/gkv494 CrossRefGoogle Scholar
  5. Joo Y, Schumacher B, Landrieu I et al (2015) Involvement of 14-3-3 in tubulin instability and impaired axon development is mediated by Tau. FASEB J 29:4133–4144.  https://doi.org/10.1096/fj.14-265009 CrossRefGoogle Scholar
  6. Jung Y-S, Zweckstetter M (2004) Mars—robust automatic backbone assignment of proteins. J Biomol NMR 30:11–23.  https://doi.org/10.1023/B:JNMR.0000042954.99056.ad CrossRefGoogle Scholar
  7. Kaplan A, Ottmann C, Fournier AE (2017) 14-3-3 adaptor protein-protein interactions as therapeutic targets for CNS diseases. Pharmacol Res 125:114–121.  https://doi.org/10.1016/j.phrs.2017.09.007 CrossRefGoogle Scholar
  8. Killoran RC, Fan J, Yang D et al (2015) Structural analysis of the 14-3-3ζ/Chibby interaction involved in Wnt/β-catenin signaling. PLoS ONE 10:e0123934.  https://doi.org/10.1371/journal.pone.0123934 CrossRefGoogle Scholar
  9. Milroy L-G, Bartel M, Henen MA et al (2015) Stabilizer-guided inhibition of protein-protein interactions. Angew Chem Int Ed 54:15720–15724.  https://doi.org/10.1002/anie.201507976 CrossRefGoogle Scholar
  10. Obsil T, Obsilova V (2011) Structural basis of 14-3-3 protein functions. Semin Cell Dev Biol 22:663–672.  https://doi.org/10.1016/j.semcdb.2011.09.001 CrossRefGoogle Scholar
  11. Stevers LM, Sijbesma E, Botta M et al (2018) Modulators of 14-3-3 protein–protein interactions. J Med Chem 61:3755–3778.  https://doi.org/10.1021/acs.jmedchem.7b00574 CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.UMR 8576 CNRS-Lille UniversityLilleFrance

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