A conserved loop in the catalytic domain of eukaryotic elongation factor 2 kinase plays a key role in its substrate specificity
A conserved loop in the catalytic domain of eukaryotic elongation factor 2 kinase plays a key role in its substrate specificity
Eukaryotic elongation factor 2 kinase (eEF2K) is the best-characterized member of the ?-kinase family. Within this group, only eEF2K and myosin heavy chain kinases (MHCKs) have known substrates. Here we have studied the roles of specific residues, selected on the basis of structural data for MHCK A and TRPM7, in the function of eEF2K. Our data provide the first information regarding the basis of the substrate specificity of ?-kinases, in particular the roles of residues in the so-called N/D loop, which appears to occupy a position in the structure of ?-kinases similar to that of the activation loop in other kinases. Several mutations in the EEF2K gene occur in tumors, one of which (Arg303Cys) is at a highly conserved residue in the N/D loop. This mutation greatly enhances eEF2K activity and may be cytoprotective. Our data support the concept that the major autophosphorylation site (Thr348 in eEF2K) docks into a binding pocket to help create the kinase-competent conformation. This is similar to the situation for MHCK A and is consistent with this being a common feature of ?-kinases.
2294-2307
Moore, C. E.
25775426-fa7e-445d-a861-9fff65c19c4f
Regufe da Mota, S.
fe39404b-e413-4834-97c6-0f2204b500a9
Mikolajek, H.
c394c255-9248-4217-ace9-4a0382bfc0c5
Proud, C.G.
c2cc50f9-4565-4d59-9dfc-aa70b9268a6e
14 April 2014
Moore, C. E.
25775426-fa7e-445d-a861-9fff65c19c4f
Regufe da Mota, S.
fe39404b-e413-4834-97c6-0f2204b500a9
Mikolajek, H.
c394c255-9248-4217-ace9-4a0382bfc0c5
Proud, C.G.
c2cc50f9-4565-4d59-9dfc-aa70b9268a6e
Moore, C. E., Regufe da Mota, S., Mikolajek, H. and Proud, C.G.
(2014)
A conserved loop in the catalytic domain of eukaryotic elongation factor 2 kinase plays a key role in its substrate specificity.
Molecular and Cellular Biology, 34 (12), .
(doi:10.1128/MCB.00388-14).
(PMID:24732796)
Abstract
Eukaryotic elongation factor 2 kinase (eEF2K) is the best-characterized member of the ?-kinase family. Within this group, only eEF2K and myosin heavy chain kinases (MHCKs) have known substrates. Here we have studied the roles of specific residues, selected on the basis of structural data for MHCK A and TRPM7, in the function of eEF2K. Our data provide the first information regarding the basis of the substrate specificity of ?-kinases, in particular the roles of residues in the so-called N/D loop, which appears to occupy a position in the structure of ?-kinases similar to that of the activation loop in other kinases. Several mutations in the EEF2K gene occur in tumors, one of which (Arg303Cys) is at a highly conserved residue in the N/D loop. This mutation greatly enhances eEF2K activity and may be cytoprotective. Our data support the concept that the major autophosphorylation site (Thr348 in eEF2K) docks into a binding pocket to help create the kinase-competent conformation. This is similar to the situation for MHCK A and is consistent with this being a common feature of ?-kinases.
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Accepted/In Press date: 27 March 2014
Published date: 14 April 2014
Organisations:
Molecular and Cellular
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Local EPrints ID: 384631
URI: http://eprints.soton.ac.uk/id/eprint/384631
ISSN: 0270-7306
PURE UUID: 5e8ff537-237e-4968-9c22-624ecd23125d
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Date deposited: 03 Dec 2015 15:44
Last modified: 14 Mar 2024 22:02
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Author:
C. E. Moore
Author:
S. Regufe da Mota
Author:
C.G. Proud
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