Model of eukaryotic translation initiation. The first step of
translation initiation is the binding of a TC composed of eIF2, GTP, and
Met-tRNAMeti to the 40 S ribosomal subunit forming the
43 S PIC. TC may bind the 40 S subunit as part of the MFC along with eIF1,
eIF5, and eIF3. eIF1A also binds and facilitates MFC recruitment. The N- and
C-terminal tails of eIF1 and eIF1A are represented in green and
pink, respectively. Although their locations in the complex are not
known, some proposed interactions are shown here. The PIC then binds mRNA with
the help of eIF3, the eIF4F complex, eIF4B, and PABP. For clarity, these
factors are not shown. The complex scans the mRNA for the start codon. During
this time, GTP bound to eIF2 can be hydrolyzed with the help of eIF5, but this
reaction is reversible because phosphate is not released. During the scanning
process, the PIC is in an open state, which is in equilibrium with a closed
state that is not capable of scanning but is able to investigate the codon in
the P-site. In this figure, the closed state is represented by a
lock, holding the mRNA in place. When an AUG codon is identified in
the P-site, the equilibrium shifts toward the closed state. eIF1 dissociates
from the 40 S ribosome, and the phosphate ion bound to eIF2 can now be
released, making hydrolysis irreversible and committing the PIC to initiate
translation at the codon currently in the P-site. After dissociation from the
ribosome, eIF1 may remain bound to the PIC through an interaction with eIF3
(29). After eIF2·GDP
and eIF5 dissociate, the 60 S subunit joins the 40 S subunit with the help of
the GTPase eIF5B. The 80 S initiation complex is now ready to begin the
elongation phase of translation. Factors in this figure are not drawn to scale
to make the smaller factors visible.