Eukaryotic translation initiation is controlled by cooperativity effects within ternary complexes of 4E-BP1, eIF4E,and the mRNA 5′ cap |
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Authors: | Anna Modrak-Wojcik Michal Gorka Katarzyna Niedzwiecka Konrad Zdanowski Joanna Zuberek Anna Niedzwiecka Ryszard Stolarski |
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Institution: | 1. Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, 93 Zwirki & Wigury St., 02-089 Warszawa, Poland;2. Institute of Biochemistry & Biophysics, Polish Academy of Sciences, 5A Pawinskiego St., 02-106 Warszawa, Poland;3. Institute of Chemistry, University of Natural Sciences and Humanities, 3 Maja 54 St., 08-110 Siedlce, Poland;4. Laboratory of Biological Physics, Institute of Physics, Polish Academy of Sciences, 32/46 Lotnikow Ave., 02-668 Warszawa, Poland |
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Abstract: | Initiation is the rate-limiting step during mRNA 5′ 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. |
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Keywords: | 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 |
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