Eukaryotic translation initiation is controlled by cooperativity effects within ternary complexes of 4E-BP1, eIF4E, and the mRNA 5鈥?cap
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- 作者：Anna Modrak-Wojcik ; Michal Gorka ; Katarzyna Niedzwiecka ; Konrad Zdanowski ; Joanna Zuberek ; Anna Niedzwiecka ; Ryszard Stolarski
- 关键词：eIF4E ; eukaryotic initiation factor 4E ; 4E-BP1 ; 4E binding protein 1 ; m7GTP ; 7-methylguanosine 5&prime ; -triphosphate ; TCEP ; tris (2-carboxyethyl) phosphine HCl ; DB ; dialysis buffer ; SPR ; surface plasmon resonance ; TFA ; trifluoroacetic acid
- 刊名：FEBS Letters
- 出版年：11 December, 2013
- 年：2013
- 卷：587
- 期：24
- 页码：3928-3934
- 全文大小：1249 K
文摘
Initiation is the rate-limiting step during mRNA 5鈥?cap-dependent translation, and thus a target of a strict control in the eukaryotic cell. It is shown here by analytical ultracentrifugation and fluorescence spectroscopy that the affinity of the human translation inhibitor, eIF4E-binding protein (4E-BP1), to the translation initiation factor 4E is significantly higher when eIF4E is bound to the cap. The 4E-BP1 binding stabilizes the active eIF4E conformation and, on the other hand, can facilitate dissociation of eIF4E from the cap. These findings reveal the particular allosteric effects forming a thermodynamic cycle for the cooperative regulation of the translation initiation inhibition.