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Eukaryotic Initiation of Protein Synthesis

eIF4F formation and ribosome recruitment. eIF4E (1) is incorporated into the eIF4F complex (2). Through eIF4E, eIF4F binds to the mRNA 5' cap structure (3). eIF4A (along with cofactor eIF4B) unwinds cap-proximal mRNA secondary structure in an ATP-dependent manner (4). The 40S ribosomal subunit bound to eIF3 (and to eIF1A and the ternary complex of eIF2-GTP-met-tRNAi) is recruited to the single-stranded mRNA through eIF4G (5). Not shown here is the interaction of eIF4G with poly A binding protein at the 3' end of the mRNA. Further addition of the 60S ribosomal subunit requires GTP hydrolysis by eIF5B and eIF2 (assisted by eIF5) and release of all the initiation factors.