Structural motifs in eIF4G and 4E-BPs modulate their binding to eIF4E to regulate translation initiation in yeast

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• Cap-dependent translation initiation is crucial for protein synthesis in eukaryotes.
• This process involves the interaction between eukaryotic initiation factor 4G (eIF4G) and the cap-binding protein eIF4E.
• 4E-binding proteins (4E-BPs) regulate this interaction by competing with eIF4G, thereby repressing translation.

Purpose of the Study:

• To investigate the structural basis of eIF4E recognition by 4E-BPs and eIF4G in fungi.
• To compare the molecular mechanisms of translation regulation between fungi and metazoans.
• To identify conserved and specialized features in eukaryotic translation initiation.

Main Methods:

• X-ray crystallography was used to determine the structures of yeast eIF4E bound to 4E-BPs (p20 and Eap1p).
• Crystal structures of a fungal eIF4E-eIF4G complex were also obtained.
• Comparative structural analysis was performed to understand conserved and divergent recognition principles.

Main Results:

• The core principles of eIF4E molecular recognition by translational activators and repressors are highly conserved across eukaryotes.
• Structural insights reveal conserved bipartite recognition modes involving dorsal and lateral surfaces of eIF4E.
• Fungal systems exhibit specialized structural motifs that modulate the affinity of protein-protein interactions, fine-tuning translation initiation.

Conclusions:

• Despite mechanistic differences, the fundamental molecular recognition of eIF4E is conserved between fungi and metazoans.
• Specialized structural motifs in fungi play a critical role in regulating the affinity of interactions involved in cap-dependent translation.
• This study provides a deeper understanding of the evolutionary conservation and diversification of translation regulation in eukaryotes.