Fig. 6. Proposed models for eIF4A-mediated PIC conformational change that unifies ribosome recruitment, scanning, and start codon selection.

In the absence of eIF4A, the closed PIC conformation leads to reduced mRNA loading, delayed PIC scanning, and increased stringency of start codon selection. In the presence of eIF4A (orange triangle), multiple cycles of ATP hydrolysis lead to open conformation of PIC that facilitates slot-in mRNA loading, bi-directional PIC scanning, and selection of suboptimal start codons (empty red star).