Protein Science, Vol 7, Issue 7 1639-1642, Copyright © 1998 by Cold Spring Harbor Laboratory Press

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The interaction of eIF4E with 4E-BP1 is an induced fit to a completely disordered protein

C. M. FLETCHER and G. WAGNER
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115

4E binding protein 1 (4E-BP1) inhibits translation by binding to the initiation factor eIF4E and is mostly or completely unstructured in both free and bound states. We wished to determine whether the free protein has local structure that could be involved in eIF4E binding. Assignments were obtained using double and triple resonance NMR methods. Residues 4-10, 43-46, and 56-65 could not be assigned, primarily because of a high degree of (1)H and (15)N chemical shift overlap. Steady-state {(1)H}-(15)N NOEs were measured for 45 residues in the assigned regions. Except for the two C-terminal residues, the NOEs were between -0.77 and -1.14, indicating a high level of flexibility. Furthermore, the {(1)H}-(15)N NOE spectrum recorded with presaturation contained no strong positive signals, making it likely that no other residues have positive or smaller negative NOEs. This implies that 4E-BP1 has no regions of local order in the absence of eIF4E. The interaction therefore appears to be an induced fit to a completely disordered protein molecule.
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