Elongation factor 2 kinase

From Wikipedia, the free encyclopedia
Jump to: navigation, search
eukaryotic elongation factor-2 kinase
Identifiers
EC number 2.7.11.20
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

In enzymology, an elongation factor 2 kinase (EC 2.7.11.20) is an enzyme that catalyzes the chemical reaction

ATP + [elongation factor 2] \rightleftharpoons ADP + [elongation factor 2] phosphate

Thus, the two substrates of this enzyme are ATP and elongation factor 2, whereas its two products are ADP and elongation factor 2 phosphate.

Nomenclature[edit]

This enzyme belongs to the family of transferases, specifically those transferring a phosphate group to the sidechain oxygen atom of serine or threonine residues in proteins (protein-serine/threonine kinases). The systematic name of this enzyme class is ATP:[elongation factor 2] phosphotransferase. Other names in common use include Ca/CaM-kinase III, calmodulin-dependent protein kinase III, CaM kinase III, eEF2 kinase, eEF-2K, eEF2K, EF2K, and STK19.

Function[edit]

The only known physiological substrate of eEF-2K is eEF-2. Phosphorylation of eEF-2 at Thr-56 by eEF-2K leads to inhibition of the elongation phase of protein synthesis. Phosphorylation of Thr-56 is thought to reduce the affinity of eEF-2 for the ribosome, thereby slowing down the overall rate of elongation.[1] However, there is growing evidence to suggest that translation of certain mRNAs is actually increased by phosphorylatoin of eEF-2 by eEF-2K, especially in a neuronal context.[2]

Activation[edit]

The activity of eEF-2K is dependent on calcium and calmodulin. Activation of eEF-2K proceeds by a sequential two-step mechanism. First, calcium-calmodulin binds with high affinity to activate the kinase domain, triggering rapid autophosphorylation of Thr-348.[3][4] In the second step, autophosphorylation of Thr-348 leads to a conformational change in the kinase likely supported by the binding of phospho-Thr-348 to an allosteric phosphate binding pocket in the kinase domain. This increases the activity of eEF-2K against its substrate, elongation factor 2.[4]

eEF-2K can gain calcium-independent activity through autophosphorylation of Ser-500. However, calmodulin must remain bound to the enzyme for its activity to be sustained.[3]

References[edit]

  1. ^ Ryazanov AG, Shestakova EA, Natapov PG (1988 Jul 14). "Phosphorylation of elongation factor 2 by EF-2 kinase affects rate of translation.". Nature 334 (6178): 170–3. PMID 3386756. 
  2. ^ Heise C, Gardoni F, Culotta L, di Luca M, Verpelli C, Sala C (2014). "Elongation factor-2 phosphorylation in dendrites and the regulation of dendritic mRNA translation in neurons.". Frontiers in cellular neuroscience 8: 35. PMID 24574971. 
  3. ^ a b Tavares CD, O'Brien JP, Abramczyk O, Devkota AK, Shores KS, Ferguson SB, Kaoud TS, Warthaka M, Marshall KD, Keller KM, Zhang Y, Brodbelt JS, Ozpolat B, Dalby KN (2012 Mar 20). "Calcium/calmodulin stimulates the autophosphorylation of elongation factor 2 kinase on Thr-348 and Ser-500 to regulate its activity and calcium dependence.". Biochemistry 51 (11): 2232–45. PMID 22329831. 
  4. ^ a b Tavares CD, Ferguson SB, Giles DH, Wang Q, Wellmann RM, O'Brien JP, Warthaka M, Brodbelt JS, Ren P, Dalby KN (2014 Aug 22). "The molecular mechanism of eukaryotic elongation factor 2 kinase activation.". The Journal of biological chemistry 289 (34): 23901–16. PMID 25012662. 

Further reading[edit]