Mediator subunit Med15 dictates the conserved “fuzzy” binding mechanism of yeast transcription activators Gal4 and Gcn4

Abstract The acidic activation domain (AD) of yeast transcription factor Gal4 plays a dual role in repression and through binding to Gal80 repressor Mediator subunit Med15. function arises from two hydrophobic regions within the 40-residue AD. We show by NMR that each AD region binds Med15 using “fuzzy” protein interface. Remarkably, comparison chemical shift perturbations shows Gcn4, intrinsically disordered ADs different sequence, interact nearly identically with finding sequence use an identical fuzzy mechanism common sequence-independent for AD-Mediator binding, similar interactions cloud. In contrast, same interacts strongly via distinct structured complex, implying partner dictates type protein–protein interaction.