Architecture of human translation initiation factor 3

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• Eukaryotic translation initiation factor 3 (eIF3) is crucial for initiating protein synthesis.
• It organizes the formation of the 43S preinitiation complex, a key step in translation.
• Understanding eIF3's structure is vital for comprehending translation regulation.

Purpose of the Study:

• To elucidate the molecular organization of the ten human eIF3 subunits.
• To compare the structure of eIF3 with other cellular complexes.
• To identify interactions of eIF3 subunits with other translation factors.

Main Methods:

• Genetic tag visualization by electron microscopy was employed.
• Structural comparisons were made with the proteasome lid.
• Interactions between eIF3 subunits and initiation factors (eIF1, eIF1A) were investigated.

Main Results:

• A ten-subunit human eIF3 complex was visualized, featuring an octameric core.
• eIF3 shares structural resemblance with the proteasome lid, indicating conserved architecture.
• Subunits a and c interact with eIF1 and eIF1A, influencing start codon selection.
• Subunit j interacts with the eIF3 octameric core, modulating mRNA interactions.

Conclusions:

• Human eIF3 possesses a conserved architecture with an octameric core.
• This structure scaffolds essential translation initiation factors, including those controlling start codon accuracy.
• eIF3 plays a significant role in regulating protein synthesis in higher eukaryotes.