The protein RLI is known to have an essential, probably catalytic role in the formation of initiation complexes as well.
eIF4G is a scaffolding protein that interacts with eIF3 (see below), as well as the other members of the eIF4F complex. eIF4A - an RNA helicase - is important for resolving any secondary structures the mRNA transcript may form. eIF4E binds the 5' cap of the mRNA and the rate-limiting step for cap-dependent translation.
eIF4B contains two RNA binding domains - one non-specific interacts with mRNA, while the second specifically binds the 18S portion of the small ribosomal subunit. It acts as an anchor, as well as a critical co-factor for eIF4A. It is a substrate of S6K and when phosphorylated it promotes the formation of the pre-initiation complex.
eIF1, eIF1A, and eIF3, all bind to the ribosome subunit-mRNA complex. They have been implicated in preventing the large ribosomal subunit from binding the small subunit before it is ready to commence elongation.
In mammals eIF3 is the largest scaffolding initiation factor made up of 13 subunits (a-m). It is roughly ~750 kDa and it controls the assembly of 40S ribosomal subunit on mRNA that have a 5' cap or an IRES. eIF3 uses the eIF4F complex or IRES (Internal Ribosomal Entry Site) from viruses to position the mRNA strand near the exit site of the 40S ribosome subunit thus promoting the assembly of the pre-initiation complex.
In many cancers eIF3 is overexpressed. Under serum deprived conditions (inactive state) eIF3 is bound to S6K1. On stimulation either by mitogens, growth factors or drugs mTOR/Raptor complex gets activated and in turn binds and phosphorylates S6K1 on T389 (linker region) causing a conformational change that causes the kinase S6K1 to dissociate from eIF3. The T389 phosphorylated S6k1 is then further phosphorylated by PDK1 on T229. This second phosphorylation fully activates the S6K1 kinase which can then phosphorylate eIF4B, S6 and other protein targets.
eIF2 has three subunits, eIF2-α, β, and γ. The former is of particular importance for cells which may need to turn off protein synthesis globally. When phosphorylated, it sequesters eIF2B (not to be confused with beta), a GEF. Without this GEF, GDP cannot be exchanged for GTP, and translation is repressed.
eIF2α-induced translation repression occurs in reticulocytes when starved for iron. Additionally, protein kinase R (PKR) phosphorylates eIF2α when dsRNA is detected in many multicellular organisms, leading to cell death.