The interaction of eIF4E with 4E‐BP1 is an induced fit to a completely disordered protein
- 1 July 1998
- journal article
- Published by Wiley in Protein Science
- Vol. 7 (7), 1639-1642
- https://doi.org/10.1002/pro.5560070720
Abstract
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 1H and 15N chemical shift overlap. Steady‐state {1H}−15N 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 {1H}−15N 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‐BPI 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.Keywords
This publication has 20 references indexed in Scilit:
- 4E Binding Proteins Inhibit the Translation Factor eIF4E without Folded StructureBiochemistry, 1998
- NMR analysis of main-chain conformational preferences in an unfolded fibronectin-binding proteinJournal of Molecular Biology, 1997
- Induced α Helix in the VP16 Activation Domain upon Binding to a Human TAFScience, 1997
- The importance of being unfoldedNature, 1997
- The C-terminal half of the anti-sigma factor, FlgM, becomes structured when bound to its target, σ28Nature Structural & Molecular Biology, 1997
- An Optimized 3D NOESY–HSQCJournal of Magnetic Resonance, Series B, 1996
- Yeast heat shock transcription factor N‐terminal activation domains are unstructured as probed by heteronuclear NMR spectroscopyProtein Science, 1996
- Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap functionNature, 1994
- Enhanced-Sensitivity Triple-Resonance Spectroscopy with Minimal H2O SaturationJournal of Magnetic Resonance, Series A, 1994
- Backbone Dynamics of a Free and a Phosphopeptide-Complexed Src Homology 2 Domain Studied by 15N NMR RelaxationBiochemistry, 1994