eIF4Gs

eIF4Gs are a family of scaffolding proteins that play a crucial role in the initiation of eukaryotic protein synthesis. They are key components of the eIF4F complex, which is responsible for recognizing and binding to the messenger RNA (mRNA) cap structure. This cap binding is a critical first step for ribosomes to assemble on the mRNA and begin translation.

There are three main isoforms of eIF4G in mammals: eIF4G1, eIF4G2, and eIF4G3. Each isoform has distinct roles and expression patterns, although they share significant structural and functional similarities. eIF4G1 is generally considered the primary isoform involved in cap-dependent translation. eIF4G2, also known as DAP5, has a more complex regulatory role and can promote cap-independent translation under certain conditions. eIF4G3 is less well-characterized but appears to contribute to translation initiation.

The structure of eIF4G proteins includes multiple protein-binding domains. These domains allow eIF4G to interact with other translation factors, such as eIF4E (the cap-binding protein), eIF4A (an RNA helicase), and the poly(A)-binding protein (PABP). This intricate network of interactions is essential for efficiently recruiting ribosomes to the mRNA and unwinding secondary structures in the mRNA that might impede translation.

Dysregulation of eIF4G function has been implicated in various cellular processes and diseases, including cancer. Its central role in controlling protein synthesis makes it a target for cellular signaling pathways and a potential therapeutic target.