eukaryotic 43S preinitiation complex

Definition

Target type: cellularcomponent

A protein complex composed of the 40S ribosomal subunit plus eIF1, eIF1A, eIF3, eIF5, and eIF2-GTP-bound methionyl-initiator methionine tRNA. [GOC:hjd, PMID:15145049, PMID:16510876, PMID:25742741, PMID:29735639]

The eukaryotic 43S preinitiation complex (PIC) is a large, multi-protein assembly that initiates translation by binding to the 5' cap of mRNA and scanning for the start codon. The core components of the 43S PIC include the 40S ribosomal subunit, the eukaryotic initiation factors eIF1, eIF1A, eIF3, eIF5, and the ternary complex (TC) composed of eIF2, GTP, and the initiator methionine tRNA (Met-tRNAi).

The 40S ribosomal subunit is the smaller of the two ribosomal subunits in eukaryotic cells and plays a crucial role in translation initiation. It contains a small ribosomal RNA (rRNA) molecule, known as 18S rRNA, and approximately 33 ribosomal proteins.

eIF1 is a small protein that binds to the 40S subunit and promotes the correct positioning of the initiator tRNA in the P-site of the ribosome.

eIF1A, similar to eIF1, also binds to the 40S subunit and promotes the correct positioning of the initiator tRNA in the P-site.

eIF3 is a large, multi-subunit complex that interacts with the 40S subunit, preventing premature association with the 60S subunit and facilitating the recruitment of the TC to the 40S subunit.

eIF5 is a GTPase-activating protein (GAP) that stimulates the hydrolysis of GTP bound to eIF2, promoting the release of eIF2 from the 43S PIC.

The ternary complex (TC) consists of eIF2, GTP, and the initiator methionine tRNA (Met-tRNAi). eIF2 is a GTPase that binds to Met-tRNAi and delivers it to the 40S subunit.

The assembly of the 43S PIC occurs in a stepwise manner:

1. eIF1, eIF1A, and eIF3 bind to the 40S subunit.
2. The TC binds to the 40S subunit, bringing the initiator tRNA to the P-site.
3. The 43S PIC then binds to the 5' cap of mRNA.
4. The 43S PIC scans along the mRNA, searching for the AUG start codon.
5. Once the AUG codon is found, eIF5 promotes the hydrolysis of GTP, leading to the release of eIF2 and the formation of the 48S initiation complex.

The 43S PIC is a dynamic complex that undergoes conformational changes throughout the initiation process, ensuring accurate and efficient translation initiation. Its precise composition and interactions with other factors regulate the translation of specific mRNAs, contributing to the regulation of gene expression in eukaryotic cells.'
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Proteins (1)

Compounds (1)