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. 2014 Sep 2;5:4790. doi: 10.1038/ncomms5790

Figure 6. eIF4G competes with 4E-BPs when their binding to the lateral surface of eIF4E is impaired.

Figure 6

(a,b) Purified complexes containing SHN-tagged eIF4E bound to either eIF4G or the indicated 4E-BPs were incubated with MBP or MBP-eIF4G-GB1. The amount of eIF4G or 4E-BP proteins that were associated with eIF4E was determined by pull down using Strep-Tactin beads. The complexes contained GST-eIF4G (residues 578–650), GST-CUP (residues 311–440), GST-Thor (full length) or GST-4E-T (residues 1–58). (c) Competition model: eIF4E (blue circle) contains a dorsal and a lateral surface that bind to the C and NC motifs of 4E-BPs (shown in orange), respectively. The dorsal surface also binds to the canonical motif of eIF4G (shown in green). The eIF4E lateral binding surface provides a docking site for the non-canonical motifs of 4E-BPs when eIF4G is bound to the dorsal surface of eIF4E via its canonical motif (1). After docking, 4E-BPs displace eIF4G from the dorsal surface of eIF4E and repress translation (2). Phosphorylation (P) of 4E-BPs destabilizes their association with eIF4E (3). Therefore, eIF4G can bind to eIF4E and translation resumes (4). In humans, 4E-BP1–3 the phosphorylation sites are located in the linker region between the 4E-BMs and in the sequences N-terminal to the canonical motif (not shown). Dephosphorylation of 4E-BPs is required for binding to eIF4E (5). Symbols are as in Fig. 3e.