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

Abstract

The intrinsically disordered acidic activation domain (AD) of the yeast transcription factor Gal4 acts through binding to the Med15 subunit of the Mediator complex. Here, the authors show that Gal4 interacts with Med15 through an identical fuzzy binding mechanism as Gcn4 AD, which has a different sequence, revealing a common sequence-independent mechanism for AD-Mediator binding. In contrast, Gal4 AD binds to the Gal80 repressor as a structured polypeptide, which strongly suggests that the structured binding partner dictates the type of protein–protein interaction for an intrinsically disordered protein.