2WH0

Recognition of an intrachain tandem 14-3-3 binding site within protein kinase C epsilon

Summary for 2WH0

• Entry DOI: 10.2210/pdb2wh0/pdb
• Related: 1IB1 1QJA 1QJB 2C1J 2C1N
• Descriptor: 14-3-3 PROTEIN ZETA/DELTA, PROTEIN KINASE C EPSILON TYPE, NPKC-EPSILON, TRIETHYLENE GLYCOL, ... (5 entities in total)
• Functional Keywords: tandem binding, phosphoprotein, signaling protein, 14-3-3, cytoplasm, acetylation, pkc epsilon
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm: P63104
• Total number of polymer chains: 6
• Total formula weight: 118756.39

Authors

Kostelecky, B.,Saurin, A.T.,Purkiss, A.,Parker, P.J.,McDonald, N.Q. (deposition date: 2009-04-28, release date: 2009-08-18, Last modification date: 2024-10-16)

Primary citation

Kostelecky, B.,Saurin, A.T.,Purkiss, A.,Parker, P.J.,Mcdonald, N.Q.
Recognition of an Intra-Chain Tandem 14-3-3 Binding Site within Pkc Epsilon.
Embo Rep., 10:983-, 2009

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.

PubMed: 19662078
DOI: 10.1038/EMBOR.2009.150

Experimental method

X-RAY DIFFRACTION (2.25 Å)