Regulation of eukaryotic initiation factor eIF2B.

Abstract

The initiation of mRNA translation requires the recruitment to the ribosome of the initiator methionyl-tRNA (Met-tRNAi). This is mediated by initiation factor-2 (eIF2), a heterotrimeric protein of subunits α-γ, of which the γ binds guanine nucleotides (Fig. 1). eIF2 can only interact with Met-tRNAi when it is in its GTP-bound form. The GTP molecule is hydrolysed late in the initiation process and eIF2 is released from the ribosome as a complex with GDP, which is inactive in binding Met-tRNAi. To enable eIF2 to participate further in translation initiation, the GDP must be released and replaced by GTP, a process termed guanine nucleotide exchange. The off-rate of GDP bound to eIF2 is very slow, and a protein factor (a guanine nucleotide exchange factor) is required to accelerate this process and facilitate the regeneration of active eIF2-GTP for subsequent rounds of translation initiation. This guanine nucleotide exchange factor is eIF2B (Fig. 1.)