Mediator subunit Med15 dictates the conserved “fuzzy” binding mechanism of yeast transcription activators Gal4 and Gcn4
Lisa M. Tuttle, Derek Pacheco, Linda Warfield, Steven Hahn, Rachel E. Klevit
Received Date: 14th November 19
The acidic activation domain (AD) of yeast transcription factor Gal4 plays a dual role in both transcription repression and activation through sequence-dependent binding to Gal80 repressor and sequence-independent binding to Mediator subunit Med15. The activation function of Gal4 arises from two hydrophobic regions within the 40-residue AD. We show by NMR that each AD region binds the Mediator subunit Med15 using a “fuzzy” protein interface. Remarkably, comparison of chemical shift perturbations shows that Gal4 and Gcn4, two ADs of different sequence, interact nearly identically with Med15. The findings that two ADs of different sequence use an identical fuzzy binding mechanism shows a common sequence-independent mechanism for AD-Mediator binding, similar to interactions within a hydrophobic cloud. In contrast, the same region of Gal4 AD interacts with Gal80 via a tight structured complex, implying that the structured binding partner of an intrinsically disordered protein dictates the type of protein interaction.
Read in full at bioRxiv.
This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.