Model for the order of events of a/eIF2 binding to different ligands and the sequence of events in translation initiation. When ribosomes are limiting and the number of a/eIF2 molecules exceeds (>) that of free 30S ribosomes, the translation initiation factor may bind preferentially to the 5′-P3-end of mRNA, a situation that may occur during slow growth conditions (Hasenöhrl et al. 2008). In opposite, when the number of free ribosomes equals or exceeds (>) that of a/eIF2, which may occur during fast growth, the factor binds to ribosomes. Our data revealed that a/eIF2 binding to 30S subunits is accelerated by the aIF1 and aIF1A. Next, Met-tRNAiMet is recruited by a/eIF2 being part of the 30S•aIF1•aIF1A•a/eIF2-GTP complex. It remains to be shown whether canonical mRNAs are recruited to the initiation complex before or after Met-tRNAiMet binding. In the next step, the correct start-codon/anti-codon interaction is monitored by aIF1 (indicated by a blue arrow). We speculate that the Met-tRNAiMet bound in the initiation complex is especially important for the recruitment of leaderless mRNAs. In analogy to E. coli (Moll et al. 2004), we consider that a leaderless mRNA is recruited to a 70S initiation complex. The given Kd values were taken from Figures 3 and 4.
