Understanding Intramolecular Crosstalk in an Intrinsically Disordered Protein

Abstract

The interaction between N_TAIL and XD from the measles virus represents a paradigmatic example of molecular recognition between an intrinsically disordered protein and a folded partner. By binding to XD, a small portion of N_TAIL (classically denoted as MoRE) undergoes a disorder-to-order transition, populating an α-helical structure, while the reminder of the protein remains disordered. Here, we demonstrate an unexpected crosstalk between such a disordered region and the adjacent molecular recognition element (MoRE). This result was obtained by producing a series of truncation and site-directed variants of N_TAIL while measuring the effects on the kinetics of folding and binding. We show that the disordered region of N_TAIL exerts its inhibitory role by slowing the folding step of the MoRE, thereby tuning the affinity of the interaction.