Structure of a human 48<i>S</i> translational initiation complex.

Abstract

A key step in translational initiation is the recruitment of the 43<i>S</i> preinitiation complex by the cap-binding complex [eukaryotic initiation factor 4F (eIF4F)] at the 5' end of messenger RNA (mRNA) to form the 48<i>S</i> initiation complex (i.e., the 48<i>S</i>). The 48<i>S</i> then scans along the mRNA to locate a start codon. To understand the mechanisms involved, we used cryo-electron microscopy to determine the structure of a reconstituted human 48<i>S</i> The structure reveals insights into early events of translation initiation complex assembly, as well as how eIF4F interacts with subunits of eIF3 near the mRNA exit channel in the 43<i>S</i> The location of eIF4F is consistent with a slotting model of mRNA recruitment and suggests that downstream mRNA is unwound at least in part by being "pulled" through the 40<i>S</i> subunit during scanning.