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PDBsum entry 5j8h
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Metal binding protein/transferase
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PDB id
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5j8h
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References listed in PDB file
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Key reference
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Title
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Structural basis for the recognition of eukaryotic elongation factor 2 kinase by calmodulin.
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Authors
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K.Lee,
S.Alphonse,
A.Piserchio,
C.D.Tavares,
D.H.Giles,
R.M.Wellmann,
K.N.Dalby,
R.Ghose.
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Ref.
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Structure, 2016,
24,
1441-1451.
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PubMed id
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Abstract
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Binding of Ca(2+)-loaded calmodulin (CaM) activates eukaryotic elongation factor
2 kinase (eEF-2K) that phosphorylates eEF-2, its only known cellular target,
leading to a decrease in global protein synthesis. Here, using an eEF-2K-derived
peptide (eEF-2KCBD) that encodes the region necessary for its CaM-mediated
activation, we provide a structural basis for their interaction. The striking
feature of this association is the absence of Ca(2+) from the CaM C-lobe sites,
even under high Ca(2+) conditions. eEF-2KCBD engages CaM largely through the C
lobe of the latter in an anti-parallel 1-5-8 hydrophobic mode reinforced by a
pair of unique electrostatic contacts. Sparse interactions of eEF-2KCBD with the
CaM N lobe results in persisting inter-lobe mobility. A conserved eEF-2K residue
(W85) anchors it to CaM by inserting into a deep hydrophobic cavity within the
CaM C lobe. Mutation of this residue (W85S) substantially weakens interactions
between full-length eEF-2K and CaM in vitro and reduces eEF-2 phosphorylation
in cells.
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