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Structural studies on the interaction between eukaryotic elongation factor 2 kinase (eEF2K) and calmodulin (CaM)

Structural studies on the interaction between eukaryotic elongation factor 2 kinase (eEF2K) and calmodulin (CaM)
Structural studies on the interaction between eukaryotic elongation factor 2 kinase (eEF2K) and calmodulin (CaM)
Eukaryotic elongation factor 2 kinase (eEF2K) critically regulates translation elongation by controlling the activity of eEF2, which catalyses the translocation reaction of the ribosome. eEF2K phosphorylates eEF2 and prevents its binding to the ribosome to inhibit translation elongation.
eEF2K is activated by elevated Ca2+ levels via calmodulin (CaM), although the molecular mechanism of activation is not understood. A conserved region at the N-terminus of eEF2K has been shown to be a key interaction site for CaM.
A peptide corresponding to the CaM binding region of eEF2K (eEF2K82-100) as well as longer eEF2K fragments to represent the full-length protein have been studied to dissect the molecular mechanism of eEF2K activation by Ca2+/CaM. Nuclear magnetic resonance (NMR) spectroscopy has been used to determine the binding site and the mechanism of peptide recognition and the three-dimensional solution structure of the Ca2+/CaM: eEF2K82-100 complex has been elucidated. These investigations revealed important roles for particular residues within the CaM binding region of eEF2K and in CaM itself and also resulted in a model for eEF2K activation that involves residues in the kinase domain, as well as the CaM binding region. The elucidation of this protein complex structure provides a vital tool in the study of eEF2K function, critical in cancer biology.
Hooper, Kelly
33ca34c7-d1b7-421b-8a0a-a790bc907365
Hooper, Kelly
33ca34c7-d1b7-421b-8a0a-a790bc907365
Werner, Jorn
1b02513a-8310-4f4f-adac-dc2a466bd115

(2015) Structural studies on the interaction between eukaryotic elongation factor 2 kinase (eEF2K) and calmodulin (CaM). University of Southampton, Biological Sciences, Doctoral Thesis, 343pp.

Record type: Thesis (Doctoral)

Abstract

Eukaryotic elongation factor 2 kinase (eEF2K) critically regulates translation elongation by controlling the activity of eEF2, which catalyses the translocation reaction of the ribosome. eEF2K phosphorylates eEF2 and prevents its binding to the ribosome to inhibit translation elongation.
eEF2K is activated by elevated Ca2+ levels via calmodulin (CaM), although the molecular mechanism of activation is not understood. A conserved region at the N-terminus of eEF2K has been shown to be a key interaction site for CaM.
A peptide corresponding to the CaM binding region of eEF2K (eEF2K82-100) as well as longer eEF2K fragments to represent the full-length protein have been studied to dissect the molecular mechanism of eEF2K activation by Ca2+/CaM. Nuclear magnetic resonance (NMR) spectroscopy has been used to determine the binding site and the mechanism of peptide recognition and the three-dimensional solution structure of the Ca2+/CaM: eEF2K82-100 complex has been elucidated. These investigations revealed important roles for particular residues within the CaM binding region of eEF2K and in CaM itself and also resulted in a model for eEF2K activation that involves residues in the kinase domain, as well as the CaM binding region. The elucidation of this protein complex structure provides a vital tool in the study of eEF2K function, critical in cancer biology.

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Published date: 1 June 2015
Organisations: University of Southampton, Centre for Biological Sciences

Identifiers

Local EPrints ID: 379476
URI: http://eprints.soton.ac.uk/id/eprint/379476
PURE UUID: 4db89af4-3b8e-41ed-8638-b78f3b6be670
ORCID for Jorn Werner: ORCID iD orcid.org/0000-0002-4712-1833

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Date deposited: 22 Jul 2015 09:26
Last modified: 06 Jun 2018 12:45

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