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PDBsum entry 2wh0
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Signaling protein
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PDB id
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2wh0
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References listed in PDB file
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Key reference
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Title
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Recognition of an intra-Chain tandem 14-3-3 binding site within pkcepsilon.
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Authors
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B.Kostelecky,
A.T.Saurin,
A.Purkiss,
P.J.Parker,
N.Q.Mcdonald.
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Ref.
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Embo Rep, 2009,
10,
983-989.
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PubMed id
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Abstract
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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.
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