Premium
The interaction of eIF4E with 4E‐BP1 is an induced fit to a completely disordered protein
Author(s) -
Fletcher C. Mark,
Wagner Gerhard
Publication year - 1998
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560070720
Subject(s) - eif4e , chemistry , crystallography , chemical shift , translation (biology) , biochemistry , messenger rna , gene
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‐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.