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

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.

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Official URL: http://dx.doi.org/10.1038/embor.2009.150

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.

Item Type: Article
Additional Information: *Sessional lecturer, no ID
School or Research Centre: Birkbeck Schools and Research Centres > School of Science > Biological Sciences
Depositing User: Administrator
Date Deposited: 04 Aug 2010 14:09
Last Modified: 17 Apr 2013 12:17
URI: http://eprints.bbk.ac.uk/id/eprint/1034

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