6nx4
From Proteopedia
Structure of the C-terminal Helical Repeat Domain of Eukaryotic Elongation Factor 2 Kinase (eEF-2K)
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 PubMedEukaryotic elongation factor 2 kinase (eEF-2K), an atypical calmodulin-activated protein kinase, regulates translational elongation by phosphorylating its substrate, eukaryotic elongation factor 2 (eEF-2), thereby reducing its affinity for the ribosome. The activation and activity of eEF-2K are critical for survival under energy-deprived conditions and is implicated in a variety of essential physiological processes. Previous biochemical experiments have indicated that the binding site for the substrate eEF-2 is located in the C-terminal domain of eEF-2K, a region predicted to harbor several alpha-helical repeats. Here, using NMR methodology we have determined the solution structure of a C-terminal fragment of eEF-2K, eEF-2K562-725 that encodes two alpha-helical repeats. The structure of eEF-2K562-725 shows signatures characteristic of TPR domains and of their SEL1-like sub-family. Further, using the analyses of NMR spectral perturbations and ITC measurements, we have localized the eEF-2 binding site on eEF-2K562-725. We find that eEF-2K562-725 engages eEF-2 with an affinity comparable to that of the full-length enzyme. Further, eEF-2K562-725 is able to inhibit the phosphorylation of eEF-2 by full-length eEF-2K in trans. Our present studies establish that eEF-2K562-725 encodes the major elements necessary to enable the eEF-2K/eEF-2 interactions. Solution Structure of the Carboxy-Terminal Tandem Repeat Domain of Eukaryotic Elongation Factor 2 Kinase and its Role in Substrate Recognition.,Piserchio A, Will N, Giles DH, Hajredini F, Dalby KN, Ghose R J Mol Biol. 2019 May 17. pii: S0022-2836(19)30290-6. doi:, 10.1016/j.jmb.2019.05.019. PMID:31108082[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Large Structures | Dalby, K N | Ghose, R | Giles, D H | Hajredini, F | Piserchio, A | Will, N | Binding domain | Eef2 | Eef2k | Elongation | Kinase | Sel1 | Tpr | Transferase | Translation
