Structural Organization of Initiation Complexes Involving the Eukaryotic Protein Synthesis Initiation Factors eIF-2 and eIF-3

Abstract

The positioning of a ribosome into the correct reading frame on the messenger RNA is a multiple step process, which in eukaryotes involves at least seven different initiation factors, eIF-1, eIF-2, eIF-3, eIF-4A, eIF-4B, eIF-4C and eIF-5 (Trachsel et al., 1977; Jagus et al., 1981). Consistent with its essential role in the overall translation, the initiation process is an important site for translational regulation. The most extensively studied regulatory systems involve initiation factor eIF-2 but other initiation factors have also been postulated to take part in regulatory mechanisms (for a review see Jackson, 1980). In vivo some of the initiation factors, including eIF-2 and eIF-3, are associated with native 40S ribosomal subparticles (Sundkvist & Staehelin, 1975) indicating that the two factors participate in the formation of initiation complexes on the small ribosomal subparticle even under physiological conditions. In order to obtain some further insight into the functional mechanisms of the initiation process we have studied the topographical arrangement of the components Involved in the organization of the active site on the 40S particle in which eIF-2, eIF-3, GTP, Met-tRNA_f and mRNA arc specifically joined together.