Eukaryotic initiation factor
prokaryotic initiation factors, reflecting the greater biological complexity of eukaryotic translation. There are at least twelve eukaryotic initiation factors, composed of many more polypeptides, and these are described below.[2]
eIF1 and eIF1AeIF1 and eIF1A both bind to the 40S ribosome subunit-mRNA complex. Together they induce an "open" conformation of the mRNA binding channel, which is crucial for scanning, tRNA delivery, and start codon recognition.[3] In particular, eIF1 dissociation from the 40S subunit is considered to be a key step in start codon recognition.[4] eIF1 and eIF1A are small proteins (13 and 16 kDa, respectively in humans) and are both components of the IF1, respectively.[5]
eIF2eIF2 is the main protein complex responsible for delivering the initiator tRNA to the P-site of the preinitiation complex, as a ternary complex containing Met- tRNAiMet and GTP (the eIF2-TC). eIF2 has specificity for the methionine-charged initiator tRNA, which is distinct from other methionine-charged tRNAs used for elongation of the polypeptide chain. The eIF2 ternary complex remains bound to the P-site while the mRNA attaches to the 40s ribosome and the complex begins to scan the mRNA. 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.[2] The hydrolysis of eIF2-GTP provides the conformational change to change the scanning complex into the 48S Initiation complex with the initiator tRNA-Met anticodon base paired to the AUG. After the initiation complex is formed the 60s subunit joins and eIF2 along with most of the initiation factors dissociate from the complex allowing the 60S subunit to bind. eIF1A and eIF5B-GTP remain bound to one another in the A site and must be hydrolyzed to be released and properly initiate elongation.[6] : 191–192
eIF2 has three subunits, eIF2- dsRNA is detected in many multicellular organisms, leading to cell death.
The proteins eIF2D are both technically named 'eIF2' but neither are part of the eIF2 heterotrimer and they seem to play unique functions in translation. Instead, they appear to be involved in specialized pathways, such as 'eIF2-independent' translation initiation or re-initiation, respectively.
eIF340S ribosomal subunit, multiple initiation factors, and cellular and viral mRNA.[7]
In mammals, eIF4F complex, or alternatively during internal initiation, an IRES , to position the mRNA strand near the exit site of the 40S ribosomal subunit, thus promoting the assembly of a functional pre-initiation complex.
In many human cancers, eIF3 subunits are overexpressed (subunits a, b, c, h, i, and m) and underexpressed (subunits e and f).[8] One potential mechanism to explain this disregulation comes from the finding that eIF3 binds a specific set of cell proliferation regulator mRNA transcripts and regulates their translation.[9] eIF3 also mediates cellular signaling through S6K1 and mTOR/Raptor to effect translational regulation.[10] eIF4The eIF4F complex is composed of three subunits: eIF4A, eIF4E, and eIF4G. Each subunit has multiple human isoforms and there exist additional eIF4 proteins: eIF4B and eIF4H. eIF4G is a 175.5-kDa scaffolding protein that interacts with poly(A) tail, potentially circularizing and activating the bound mRNA. 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. It acts as an anchor, as well as a critical co-factor for eIF4A. It is also a substrate of S6K, and when phosphorylated, it promotes the formation of the pre-initiation complex. In vertebrates, eIF4H is an additional initiation factor with similar function to eIF4B. eIF5, eIF5A and eIF5BeIF5 is a GTPase-activating protein, which helps the large ribosomal subunit associate with the small subunit. It is required for GTP-hydrolysis by eIF2. eIF5A is the eukaryotic homolog of EF-P. It helps with elongation and also plays a role in termination. EIF5A contains the unusual amino acid hypusine.[11] IF2.[12]
eIF6large subunit .
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