Recognition of an intra-chain tandem 14-3-3 binding site within PKCepsilon.
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Kostelecky B, Saurin AT, Purkiss A, Parker PJ, McDonald NQ
Recognition of an intra-chain tandem 14-3-3 binding site within PKCepsilon.
EMBO Rep. 2009 Sep;10(9):983-9. doi: 10.1038/embor.2009.150. Epub 2009 Aug 7.
- PubMed ID
- 19662078 [ View in PubMed]
- 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.