4E BINDING-PROTEINS INHIBIT THE TRANSLATION FACTOR EIF4E WITHOUT FOLDED STRUCTURE

The 4E binding proteins (4E-BP1 and 4E-BP2) inhibit translation by bin ding to the limiting, proto-oncogenic initiation factor eIF4E, 4E-BPs produced in Escherichia coli had little or no folded structure, measur ed by NMR and CD. However, these proteins inhibited translation in ret iculocyte lysate. Furthermore, they bound to isolated mouse eIF4E, sho wing a few broader, dispersed new NMR signals but no general increase in chemical shift dispersion. A peptide with the sequence of 4E-BP1 re sidues 49-68 was sufficient to bind eIF4E and to inhibit translation i n reticulocyte lysate, These results suggest that a short central regi on of the 4E-BPs is responsible for eIF4E binding and translation inhi bition while the remainder is unfolded and flexible.