Eukaryotic translation initiation factor 4E (eIF4E) is essential for efficient protein synthesis in cap-dependent translation. The protein specifically binds the cap structure at the mRNA 5’ terminus and facilitates the assembly of the mRNA with other initiation factors and the 40S ribosomal subunit. eIF4E homologues have been identified in most organisms, but their function in many cases is unknown. In mammals, there are three members of the eIF4E-family: eIF4E (eIF4E-1), 4EHP (eIF4E-2) and eIF4E-3. Previously studies showed that 4EHP binds the m⁷GTP-Sepharose, not binds eIF4G and therefore cannot stimulate translation, but instead it could be inhibit the translation of a subset mRNAs. To understand why 4EHP does not inhibit general translation, we studied the binding affinity of 4EHP for cap analogues using two methods: fluorescence titration and stopped-flow measurements. We show that 4EHP binds cap analogues m⁷GpppG, m⁷GTP with a 30, 100 lower affinity than eIF4E. Thus, 4EHP cannot compete with eIF4E for binding to the cap structure of most mRNAs.

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1. Binding affinity of Leishmania eIF4E isoforms for unique trypanosomatid cap-4 structure