Eukaryotic Initiation Factor 2B (eIF2B)

Eukaryotic initiation factor 2B (eIF2B) is a critical protein complex in eukaryotic cells that functions as a guanine nucleotide exchange factor (GEF). Its primary role is to catalyze the exchange of GDP for GTP on eukaryotic initiation factor 2 (eIF2), thereby enabling the recycling of eIF2 and sustaining the initiation phase of protein synthesis. It is a heteropentameric complex, consisting of alpha (α), beta (β), gamma (γ), delta (δ), and epsilon (ε) subunits. The activity of eIF2B is tightly regulated by phosphorylation events, particularly under cellular stress conditions via kinases that phosphorylate eIF2α, leading to reduced general protein synthesis. Mutations in eIF2B subunits are linked to severe human diseases like Vanishing White Matter Disease and Permanent Neonatal Diabetes Mellitus.

Modulation of eIF2B activity affects global protein synthesis rates.