Kostelecky, B. and Saurin, A.T. and Purkiss, Andrew G. and Parker, P.J. and McDonald, Neil Q. (2009) Recognition of an intra-chain tandem 14-3-3 binding site within PKCepsilon. EMBO Reports 10 (9), pp. 983-989. ISSN 1469-3178.
Abstract
The phosphoserine/threonine binding protein 14-3-3 stimulates the catalytic activity of protein kinase C- (PKC) by engaging two tandem phosphoserine-containing motifs located between the PKC regulatory and catalytic domains (V3 region). Interaction between 14-3-3 and this region of PKC is essential for the completion of cytokinesis. Here, we report the crystal structure of 14-3-3 bound to a synthetic diphosphorylated PKC 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 PKC. 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.
Metadata
| Item Type: | Article |
|---|---|
| Additional Information: | *Sessional lecturer, no ID |
| School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Research Centres and Institutes: | Structural Molecular Biology, Institute of (ISMB) |
| Depositing User: | Administrator |
| Date Deposited: | 04 Aug 2010 14:09 |
| Last Modified: | 02 Aug 2023 16:49 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/1034 |
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