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Recognition of an intra-chain tandem 14-3-3 binding site within PKCepsilon.

Kostelecky B, Saurin AT, Purkiss A, Parker PJ, McDonald NQ
EMBO Rep 10 983-9 (2009)
Cited: 67 times
EuropePMC logo PMID: 19662078

Abstract

The phosphoserine/threonine binding protein 14-3-3 stimulates the catalytic activity of protein kinase C-epsilon (PKCepsilon) by engaging two tandem phosphoserine-containing motifs located between the PKCepsilon regulatory and catalytic domains (V3 region). Interaction between 14-3-3 and this region of PKCepsilon is essential for the completion of cytokinesis. Here, we report the crystal structure of 14-3-3zeta bound to a synthetic diphosphorylated PKCepsilon V3 region revealing how a consensus 14-3-3 site and a divergent 14-3-3 site cooperate to bind to 14-3-3 and so activate PKCepsilon. Thermodynamic data show a markedly enhanced binding affinity for two-site phosphopeptides over single-site 14-3-3 binding motifs and identifies Ser 368 as a gatekeeper phosphorylation site in this physiologically relevant 14-3-3 ligand. This dual-site intra-chain recognition has implications for other 14-3-3 targets, which seem to have only a single 14-3-3 motif, as other lower affinity and cryptic 14-3-3 gatekeeper sites might exist.

Articles - 2wh0 mentioned but not cited (6)

  1. 14-3-3 proteins interact with a hybrid prenyl-phosphorylation motif to inhibit G proteins. Riou P, Kjær S, Garg R, Purkiss A, George R, Cain RJ, Bineva G, Reymond N, McColl B, Thompson AJ, O'Reilly N, McDonald NQ, Parker PJ, Ridley AJ. Cell 153 640-653 (2013)
  2. Recognition of an intra-chain tandem 14-3-3 binding site within PKCepsilon. Kostelecky B, Saurin AT, Purkiss A, Parker PJ, McDonald NQ. EMBO Rep 10 983-989 (2009)
  3. Structure of a 14-3-3σ-YAP phosphopeptide complex at 1.15 A resolution. Schumacher B, Skwarczynska M, Rose R, Ottmann C. Acta Crystallogr Sect F Struct Biol Cryst Commun 66 978-984 (2010)
  4. Structural Analysis of the 14-3-3ζ/Chibby Interaction Involved in Wnt/β-Catenin Signaling. Killoran RC, Fan J, Yang D, Shilton BH, Choy WY. PLoS One 10 e0123934 (2015)
  5. Exploring the binding pathways of the 14-3-3ζ protein: Structural and free-energy profiles revealed by Hamiltonian replica exchange molecular dynamics with distancefield distance restraints. Nagy G, Oostenbrink C, Hritz J. PLoS One 12 e0180633 (2017)
  6. Activity to Breast Cancer Cell Lines of Different Malignancy and Predicted Interaction with Protein Kinase C Isoforms of Royleanones. Isca VMS, Sencanski M, Filipovic N, Dos Santos DJVA, Čipak Gašparović A, Saraíva L, Afonso CAM, Rijo P, García-Sosa AT. Int J Mol Sci 21 E3671 (2020)


Reviews citing this publication (14)

  1. Structural basis of 14-3-3 protein functions. Obsil T, Obsilova V. Semin Cell Dev Biol 22 663-672 (2011)
  2. 14-3-3 Proteins in Brain Development: Neurogenesis, Neuronal Migration and Neuromorphogenesis. Cornell B, Toyo-Oka K. Front Mol Neurosci 10 318 (2017)
  3. Cardiac actions of protein kinase C isoforms. Steinberg SF. Physiology (Bethesda) 27 130-139 (2012)
  4. 14-3-3 proteins and regulation of cytoskeleton. Sluchanko NN, Gusev NB. Biochemistry (Mosc) 75 1528-1546 (2010)
  5. Tuning the signalling output of protein kinase C. Antal CE, Newton AC. Biochem Soc Trans 42 1477-1483 (2014)
  6. Oligomeric structure of 14-3-3 protein: what do we know about monomers? Sluchanko NN, Gusev NB. FEBS Lett 586 4249-4256 (2012)
  7. The 14-3-3 Proteins as Important Allosteric Regulators of Protein Kinases. Obsilova V, Obsil T. Int J Mol Sci 21 E8824 (2020)
  8. Survey of the year 2009: applications of isothermal titration calorimetry. Falconer RJ, Collins BM. J Mol Recognit 24 1-16 (2011)
  9. Dynamic multiprotein assemblies shape the spatial structure of cell signaling. Nussinov R, Jang H. Prog Biophys Mol Biol 116 158-164 (2014)
  10. Molecular insight into specific 14-3-3 modulators: Inhibitors and stabilisers of protein-protein interactions of 14-3-3. Hartman AM, Hirsch AKH. Eur J Med Chem 136 573-584 (2017)
  11. Pathways to Parkinson's disease: a spotlight on 14-3-3 proteins. Giusto E, Yacoubian TA, Greggio E, Civiero L. NPJ Parkinsons Dis 7 85 (2021)
  12. Motif co-regulation and co-operativity are common mechanisms in transcriptional, post-transcriptional and post-translational regulation. Van Roey K, Davey NE. Cell Commun Signal 13 45 (2015)
  13. A cancer-associated, genome protective programme engaging PKCε. Parker PJ, Lockwood N, Davis K, Kelly JR, Soliman TN, Pardo AL, Marshall JJT, Redmond JM, Vitale M, Silvia Martini. Adv Biol Regul 78 100759 (2020)
  14. Structural insights into the role of SHOC2-MRAS-PP1C complex in RAF activation. Bonsor DA, Simanshu DK. FEBS J 290 4852-4863 (2023)

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