Insights into the regulation of eukaryotic elongation factor 2 kinase and the interplay between its domains
Pigott, Craig R., Mikolajek, Halina, Moore, Claire E., Finn, Stephen J., Phippen, Curtis W., Werner, Jörn M. and Proud, Christopher G. (2012) Insights into the regulation of eukaryotic elongation factor 2 kinase and the interplay between its domains. Biochemical Journal, 442, (1), 105-118. (doi:10.1042/BJ20111536). (PMID:22115317).
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eEF2K (eukaryotic elongation factor 2 kinase) is a Ca2+/CaM (calmodulin)-dependent protein kinase which regulates the translation elongation machinery. eEF2K belongs to the small group of so-called 'α-kinases' which are distinct from the main eukaryotic protein kinase superfamily. In addition to the α-kinase catalytic domain, other domains have been identified in eEF2K: a CaM-binding region, N-terminal to the kinase domain; a C-terminal region containing several predicted α-helices (resembling SEL1 domains); and a probably rather unstructured 'linker' region connecting them. In the present paper, we demonstrate: (i) that several highly conserved residues, implicated in binding ATP or metal ions, are critical for eEF2K activity; (ii) that Ca2+/CaM enhance the ability of eEF2K to bind to ATP, providing the first insight into the allosteric control of eEF2K; (iii) that the CaM-binding/α-kinase domain of eEF2K itself possesses autokinase activity, but is unable to phosphorylate substrates in trans; (iv) that phosphorylation of these substrates requires the SEL1-like domains of eEF2K; and (v) that highly conserved residues in the C-terminal tip of eEF2K are essential for the phosphorylation of eEF2, but not a peptide substrate. On the basis of these findings, we propose a model for the functional organization and control of eEF2K.
|Keywords:||calmodulin (CaM), eukaryotic elongation factor 2 (eEF2), α-kinase, SEL1 domain|
|Subjects:||Q Science > QH Natural history > QH301 Biology|
|Divisions:||Faculty of Natural and Environmental Sciences > Biological Sciences
|Date Deposited:||18 Apr 2012 13:08|
|Last Modified:||26 Jul 2012 00:11|
|Contributors:||Pigott, Craig R. (Author)
Mikolajek, Halina (Author)
Moore, Claire E. (Author)
Finn, Stephen J. (Author)
Phippen, Curtis W. (Author)
Werner, Jörn M. (Author)
Proud, Christopher G. (Author)
|Date:||15 February 2012|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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