Eukaryotic initiation factor

Eukaryotic initiation factors (eIFs) are proteins or protein complexes involved in the initiation phase of eukaryotic translation. These proteins help stabilize the formation of ribosomal preinitiation complexes around the start codon and are an important input for post-transcription gene regulation. Several initiation factors form a complex with the small 40S ribosomal subunit and Met-tRNAiMet called the 43S preinitiation complex (43S PIC). Additional factors of the eIF4F complex (eIF4A, E, and G) recruit the 43S PIC to the five-prime cap structure of the mRNA, from which the 43S particle scans 5'-->3' along the mRNA to reach an AUG start codon. Recognition of the start codon by the Met-tRNAiMet promotes gated phosphate and eIF1 release to form the 48S preinitiation complex (48S PIC), followed by large 60S ribosomal subunit recruitment to form the 80S ribosome. There exist many more eukaryotic initiation factors than 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. eIF1 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. In particular, eIF1 dissociation from the 40S subunit is considered to be a key step in start codon recognition. eIF1 and eIF1A are small proteins (13 and 16 kDa, respectively in humans) and are both components of the 43S PIC. eIF1 binds near the ribosomal P-site, while eIF1A binds near the A-site, in a manner similar to the structurally and functionally related bacterial counterparts IF3 and IF1, respectively. eIF2 eIF2 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).