The eIF4F at the m7G cap at the 5′ end of mRNA (A) recruits the 43S complex of the 40S subunit with initiation factors and initiator tRNAi
Met (B) to form the 48S complex (C). eIF4F binds to the eIF3 structural core, which places eIF4E 30 to 40 nucleotides upstream of the P site of the 40S ribosomal subunit. During scanning, the mRNA is pulled through the 40S subunit [indicated by arrow in (C)], until the start codon is reached (D and E). In two alternative scenarios, eIF4F could dissociate from the cap during scanning (D), or it could stay bound resulting in the mRNA forming a loop (E). Although not part of the structure in this work, the mRNA is shown with a poly(A) tail and a PABP interacting with eIF4F to reflect the situation in vivo (39).