Eukaryotic elongation factor 2 kinase (eEF-2K) is a key modulator of the rate of protein synthesis. Activated by calcium-loaded calmodulin (Ca2+-CaM), eEF-2K phosphorylates its only known physiological substrate, eEF-2, on a specific threonine residue (Thr-56). Phosphorylated eEF-2 has reduced affinity for the ribosome, and results in a significant decrease in the rate of translation elongation. Modulation of the rate of translation elongation plays a crucial role in proteostasis – adequate regulation of protein synthesis, protein folding, and protein degradation that greatly influences cellular growth and survival. Binding of Ca2+-CaM triggers activation of eEF-2K and remains intact to facilitate the substrate phosphorylation, acting as a cofactor of the enzyme. Despite its importance, how the binding of Ca2+-CaM leads to activation remains poorly understood.
We employed various biophysical tools, such as nuclear magnetic resonance (NMR) spectroscopy and isothermal titration calorimetry (ITC), coupled with mutational strategies to characterize structural and thermodynamic nature of the binding of Ca2+-CaM onto eEF-2K. Our data clarify the roles of Ca2+ and each lobe of CaM that provide mechanistic insight into the structural regulation of eEF-2K mediated by the binding of Ca2+-CaM.
","abstract_html":"<p>Eukaryotic elongation factor 2 kinase (eEF-2K) is a key modulator of the rate of protein synthesis. Activated by calcium-loaded calmodulin (Ca<sup>2+</sup>-CaM), eEF-2K phosphorylates its only known physiological substrate, eEF-2, on a specific threonine residue (Thr-56). Phosphorylated eEF-2 has reduced affinity for the ribosome, and results in a significant decrease in the rate of translation elongation. Modulation of the rate of translation elongation plays a crucial role in proteostasis – adequate regulation of protein synthesis, protein folding, and protein degradation that greatly influences cellular growth and survival. Binding of Ca<sup>2+</sup>-CaM triggers activation of eEF-2K and remains intact to facilitate the substrate phosphorylation, acting as a cofactor of the enzyme. Despite its importance, how the binding of Ca<sup>2+</sup>-CaM leads to activation remains poorly understood.</p> <p>We employed various biophysical tools, such as nuclear magnetic resonance (NMR) spectroscopy and isothermal titration calorimetry (ITC), coupled with mutational strategies to characterize structural and thermodynamic nature of the binding of Ca<sup>2+</sup>-CaM onto eEF-2K. Our data clarify the roles of Ca<sup>2+</sup> and each lobe of CaM that provide mechanistic insight into the structural regulation of eEF-2K mediated by the binding of Ca<sup>2+</sup>-CaM.</p>","abstract_has_math":false,"creators":["Lee, Kwangwoon"],"institution":"The Graduate School and University Center of The City University of New York","degree_name":"Doctor of Philosophy","degree_level":"Doctoral","degree_discipline":"Biochemistry","degree_department":null,"school":null,"contributors":[],"advisors":["Ranajeet Ghose"],"committee_chairs":[],"committee_members":["Kevin Dalby","David Jeruzalmi","Reza Khayat","Ming-Ming Zhou"],"year":2019,"date_issued":"2019-02-01T08:00:00Z","date_published":"2019-02-01T08:00:00Z","updated_at":"2026-07-24T01:59:05Z","subjects":["Biochemistry","Biophysics","Structural Biology","calmodulin","eEF-2K","NMR","ITC"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://academicworks.cuny.edu/gc_etds/3037","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Ranajeet Ghose"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Kevin Dalby","David Jeruzalmi","Reza Khayat","Ming-Ming Zhou"]},{"key":"dc:creator","label":"Author","values":["Lee, Kwangwoon"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2021-02-01T08:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biochemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The Graduate School and University Center of The City University of New York"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biochemistry","Biophysics","Structural Biology","calmodulin","eEF-2K","NMR","ITC"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://academicworks.cuny.edu/gc_etds/3037"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Eukaryotic elongation factor 2 kinase (eEF-2K) is a key modulator of the rate of protein synthesis. Activated by calcium-loaded calmodulin (Ca2+-CaM), eEF-2K phosphorylates its only known physiological substrate, eEF-2, on a specific threonine residue (Thr-56). Phosphorylated eEF-2 has reduced affinity for the ribosome, and results in a significant decrease in the rate of translation elongation. Modulation of the rate of translation elongation plays a crucial role in proteostasis – adequate regulation of protein synthesis, protein folding, and protein degradation that greatly influences cellular growth and survival. Binding of Ca2+-CaM triggers activation of eEF-2K and remains intact to facilitate the substrate phosphorylation, acting as a cofactor of the enzyme. Despite its importance, how the binding of Ca2+-CaM leads to activation remains poorly understood.
We employed various biophysical tools, such as nuclear magnetic resonance (NMR) spectroscopy and isothermal titration calorimetry (ITC), coupled with mutational strategies to characterize structural and thermodynamic nature of the binding of Ca2+-CaM onto eEF-2K. Our data clarify the roles of Ca2+ and each lobe of CaM that provide mechanistic insight into the structural regulation of eEF-2K mediated by the binding of Ca2+-CaM.
"]},{"key":"dc:title","label":"Title","values":["Structural Studies on Calcium/calmodulin-dependent Activation of Eukaryotic Elongation Factor 2 Kinase"]}]}],"canonical_facts":{"dc:contributor.advisor":["Ranajeet Ghose"],"dc:contributor.committeemember":["Kevin Dalby","David Jeruzalmi","Reza Khayat","Ming-Ming Zhou"],"dc:creator":["Lee, Kwangwoon"],"dc:date.available":["2021-02-01T08:00:00Z"],"dc:description.abstract":["Eukaryotic elongation factor 2 kinase (eEF-2K) is a key modulator of the rate of protein synthesis. Activated by calcium-loaded calmodulin (Ca2+-CaM), eEF-2K phosphorylates its only known physiological substrate, eEF-2, on a specific threonine residue (Thr-56). Phosphorylated eEF-2 has reduced affinity for the ribosome, and results in a significant decrease in the rate of translation elongation. Modulation of the rate of translation elongation plays a crucial role in proteostasis – adequate regulation of protein synthesis, protein folding, and protein degradation that greatly influences cellular growth and survival. Binding of Ca2+-CaM triggers activation of eEF-2K and remains intact to facilitate the substrate phosphorylation, acting as a cofactor of the enzyme. Despite its importance, how the binding of Ca2+-CaM leads to activation remains poorly understood.
We employed various biophysical tools, such as nuclear magnetic resonance (NMR) spectroscopy and isothermal titration calorimetry (ITC), coupled with mutational strategies to characterize structural and thermodynamic nature of the binding of Ca2+-CaM onto eEF-2K. Our data clarify the roles of Ca2+ and each lobe of CaM that provide mechanistic insight into the structural regulation of eEF-2K mediated by the binding of Ca2+-CaM.
"],"dc:identifier":["https://academicworks.cuny.edu/gc_etds/3037"],"dc:subject":["Biochemistry","Biophysics","Structural Biology","calmodulin","eEF-2K","NMR","ITC"],"dc:title":["Structural Studies on Calcium/calmodulin-dependent Activation of Eukaryotic Elongation Factor 2 Kinase"],"thesis:degree_discipline":["Biochemistry"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Doctor of Philosophy"],"thesis:institution_name":["The Graduate School and University Center of The City University of New York"]},"updated_at":"2026-07-24T01:59:05Z"}