A conserved HEAT domain within elF4G directs assembly of the translation initiation machinery

The X-ray structure of the phylogenetically conserved middle portion of hum an eukaryotic initiation factor (eIF) 4GII has been determined at 2.4 Angst rom resolution, revealing a crescent-shaped domain consisting of ten alpha helices arranged as five HEAT repeats. Together with the ATP-dependent RNA helicase eIF4A, this HEAT domain suffices for 48S ribosomal complex formati on with a picornaviral RNA internal ribosome entry site (IRES). Structure-b ased site-directed mutagenesis was used to identify two adjacent features o n the surface of this essential component of the translation initiation mac hinery that, respectively, bind eIF4A and a picornaviral IRES. The structur al and biochemical results provide mechanistic insights into both cap-depen dent and cap-independent translation initiation.