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| | ==Structure of the C-terminal Helical Repeat Domain of Eukaryotic Elongation Factor 2 Kinase (eEF-2K)== | | ==Structure of the C-terminal Helical Repeat Domain of Eukaryotic Elongation Factor 2 Kinase (eEF-2K)== |
| - | <StructureSection load='6nx4' size='340' side='right'caption='[[6nx4]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='6nx4' size='340' side='right'caption='[[6nx4]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6nx4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NX4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NX4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6nx4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NX4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NX4 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EEF2K ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/[Elongation_factor_2]_kinase [Elongation factor 2] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.20 2.7.11.20] </span></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6nx4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nx4 OCA], [https://pdbe.org/6nx4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nx4 RCSB], [https://www.ebi.ac.uk/pdbsum/6nx4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nx4 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6nx4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nx4 OCA], [http://pdbe.org/6nx4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nx4 RCSB], [http://www.ebi.ac.uk/pdbsum/6nx4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nx4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/EF2K_HUMAN 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.<ref>PMID:14709557</ref> <ref>PMID:9144159</ref> | + | [https://www.uniprot.org/uniprot/EF2K_HUMAN 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.<ref>PMID:14709557</ref> <ref>PMID:9144159</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Eukaryotic 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.
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| - | 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<ref>PMID:31108082</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 6nx4" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Dalby, K N]] | + | [[Category: Dalby KN]] |
| - | [[Category: Ghose, R]] | + | [[Category: Ghose R]] |
| - | [[Category: Giles, D H]] | + | [[Category: Giles DH]] |
| - | [[Category: Hajredini, F]] | + | [[Category: Hajredini F]] |
| - | [[Category: Piserchio, A]] | + | [[Category: Piserchio A]] |
| - | [[Category: Will, N]] | + | [[Category: Will N]] |
| - | [[Category: Binding domain]]
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| - | [[Category: Eef2]]
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| - | [[Category: Eef2k]]
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| - | [[Category: Elongation]]
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| - | [[Category: Kinase]]
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| - | [[Category: Sel1]]
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| - | [[Category: Tpr]]
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| - | [[Category: Transferase]]
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| - | [[Category: Translation]]
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