5j8h
From Proteopedia
Structure of calmodulin in a complex with a peptide derived from a calmodulin-dependent kinase
Structural highlights
Function[EF2K_HUMAN] Threonine kinase that regulates protein synthesis by controlling the rate of peptide chain elongation. Upon activation by a variety of upstream kinases including AMPK or TRPM7, phosphorylates the elongation factor EEF2 at a single site, renders it unable to bind ribosomes and thus inactive. In turn, the rate of protein synthesis is reduced.[1] [2] Publication Abstract from PubMedBinding of Ca2+-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 Ca2+ from the CaM C-lobe sites, even under high Ca2+ 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. Structural Basis for the Recognition of Eukaryotic Elongation Factor 2 Kinase by Calmodulin.,Lee K, Alphonse S, Piserchio A, Tavares CD, Giles DH, Wellmann RM, Dalby KN, Ghose R Structure. 2016 Sep 6;24(9):1441-1451. doi: 10.1016/j.str.2016.06.015. Epub 2016 , Aug 4. PMID:27499441[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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