eEF2 (Eukaryotic Elongation Factor 2) is a crucial translation elongation factor essential for protein synthesis in all eukaryotic cells. It plays a critical role in delivering aminoacyl-tRNAs to the ribosome during the elongation phase of translation. Dysregulation of eEF2 has been strongly linked to neurodegenerative diseases including Alzheimer's, Parkinson's, and Huntington's diseases.
eEF2 is a GTP-binding protein that catalyzes the translocation of peptidyl-tRNA from the A-site to the P-site of the ribosome during protein synthesis. It is one of the most abundant cellular proteins and is essential for cell viability.
|+ **eEF2 Protein**
! Protein Name
| eEF2 Protein
! Gene
| [EEF2](/genes/eef2)
! UniProt ID
| [P13641](https://www.uniprot.org/uniprot/P13641)
! PDB IDs
| 1N2U, 1N33
! Molecular Weight
| 95.4 kDa
! Subcellular Localization
| Cytoplasm
! Protein Family
| EF-2 family
¶ Gene and Protein Structure
The EEF2 gene is located on chromosome 19p13.3 and encodes a protein of 739 amino acids. It is a highly conserved protein across eukaryotes.
¶ Protein Domains
eEF2 has several functional domains:
- N-terminal GTP-binding domain: Binds and hydrolyzes GTP
- Domain II: Interacts with tRNA
- Domain III: Contacts the ribosome
- Domain IV: C-terminal helical domain
- Switch regions: Undergo conformational changes during GTP hydrolysis
eEF2 carries out the translocation step:
- GTP-dependent binding: eEF2-GTP binds to the ribosome
- tRNA translocation: Moves peptidyl-tRNA from A-site to P-site
- GTP hydrolysis: Triggers conformational change
- Recycling: eEF2-GDP dissociates for another cycle
- Phosphorylation: eEF2 kinase phosphorylates eEF2 at Thr56
- Stress response: Phosphorylation reduces translation during stress
- Synaptic plasticity: Local translation regulation at synapses
eEF2 is highly relevant to AD pathogenesis:
- Synaptic protein synthesis: eEF2 regulates synaptic plasticity proteins
- Tau pathology: Hyperphosphorylated tau affects translation
- Memory impairment: Dysregulated eEF2 linked to memory deficits
- Therapeutic target: eEF2 kinase inhibitors show promise
In PD, eEF2 alterations include:
- Dopaminergic neurons: Vulnerable to translation dysregulation
- Alpha-synuclein: Translation changes affect protein homeostasis
- Mitochondrial proteins: eEF2 affects synthesis of mitochondrial components
- Transcription regulation: Altered translation affects gene expression
- Neuronal dysfunction: eEF2 dysregulation contributes to pathology
eEF2 is a promising therapeutic target:
- eEF2 kinase inhibitors: RXDX-103 (tamatinib) studied
- Synaptic protection: Enhancing synaptic protein synthesis
- Stress response modulators: Normalizing translation
- Phosphorylation status: eEF2 phosphorylation as disease marker
- Activity measurements: Translation rate as biomarker