In the latest issue of Nature, the Forman-Kay lab describes how the structure of an intrinsically disordered region of 4E-BP is modulated by phosphorylation.
In its non-phosphorylated state, 4E-BP2 binds eIF4E with a helical binding element to suppress cap-dependent translation initiation. Phosphorylation at T37 and T46 induces folding of residues P18–R62 into a four-stranded beta-domain that sequesters the eIF4E-binding element into a partly buried beta-strand and the additional phosphorylation sites stabilize this fold. This mechanism for phospho-regulation of the 4E-BP:eIF4E interaction exemplifies a previously unreported mode of biological regulation mediated by intrinsically disordered proteins.
