These proteins help stabilize the formation of ribosomal preinitiation complexes around the start codon and are an important input for post-transcription gene regulation.
Together they induce an "open" conformation of the mRNA binding channel, which is crucial for scanning, tRNA delivery, and start codon recognition.
Once the AUG start codon is recognized and located in the P-site, eIF5 stimulates the hydrolysis of eIF2-GTP, effectively switching it to the GDP-bound form via gated phosphate release.
eIF1A and eIF5B-GTP remain bound to one another in the A site and must be hydrolyzed to be released and properly initiate elongation.
In the case of viral infection, protein kinase R (PKR) phosphorylates eIF2α when dsRNA is detected in many multicellular organisms, leading to cell death.
The proteins eIF2A and eIF2D are both technically named 'eIF2' but neither are part of the eIF2 heterotrimer and they seem to play unique functions in translation.
eIF3 independently binds the 40S ribosomal subunit, multiple initiation factors, and cellular and viral mRNA.
It has a molecular weight of ~800 kDa and controls the assembly of the 40S ribosomal subunit on mRNA that have a 5' cap or an IRES.
eIF4A – a DEAD box RNA helicase – is important for resolving mRNA secondary structures.
eIF4B contains two RNA-binding domains – one non-specifically interacts with mRNA, whereas the second specifically binds the 18S portion of the small ribosomal subunit.