EIF2S1 Human

The eIF2 complex is composed of three non-identical subunits:

• EIF2S1 (eIF2α): The 36-kDa alpha subunit.
• EIF2S2 (eIF2β): The 38-kDa beta subunit.
• EIF2S3 (eIF2γ): The 52-kDa gamma subunit .

The primary function of eIF2α is to facilitate the binding of the initiator methionyl-tRNA to the 40S ribosomal subunit, forming a 43S pre-initiation complex (43S PIC). This process is essential for the initiation of translation, where the mRNA binds to the 43S PIC, followed by the joining of the 60S ribosomal subunit to form the 80S initiation complex .

The activity of eIF2α is tightly regulated by phosphorylation at specific serine residues (Ser-49 and Ser-52). Phosphorylation stabilizes the eIF2/GDP/eIF2B complex, preventing the exchange of GDP for GTP, thereby inhibiting the formation of the 43S PIC. This regulation is crucial for the integrated stress response (ISR), allowing cells to adapt to various stress conditions by attenuating global protein synthesis while promoting the translation of specific mRNAs .

eIF2α is a key player in the integrated stress response (ISR), which is activated in response to various stressors such as nutrient deprivation, viral infection, and oxidative stress. Phosphorylation of eIF2α leads to a global reduction in protein synthesis, conserving resources and allowing the cell to focus on stress-specific responses. Additionally, eIF2α is involved in mitophagy, a process that removes damaged mitochondria, thereby maintaining cellular health .

Mutations or dysregulation of eIF2α have been associated with various diseases, including neurodegenerative disorders, cancer, and metabolic diseases. Understanding the role of eIF2α in these conditions can provide insights into potential therapeutic targets .

Recombinant eIF2α is produced using recombinant DNA technology, allowing for the study of its structure, function, and regulatory mechanisms in a controlled environment. This has been instrumental in advancing our understanding of protein synthesis and its regulation .