The acidic transcription activator gcn4 binds the mediator subunit gal11/med15 using a simple protein interface forming a fuzzy complex.

Publication Type:

Journal Article

Source:

Molecular cell, Volume 44, Issue 6, p.942-53 (2011)

Keywords:

2011, Basic Sciences Division, Basic-Leucine Zipper Transcription Factors, Binding Sites, Center-Authored Paper, Consortium Authored Paper, Genomics Core Facility, Jan 12, January 2012, Mediator Complex, Models, Molecular, Nuclear Magnetic Resonance, Biomolecular, Protein Binding, Protein Conformation, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Scientific Imaging Core Facility, Shared Resources

Abstract:

The structural basis for binding of the acidic transcription activator Gcn4 and one activator-binding domain of the Mediator subunit Gal11/Med15 was examined by NMR. Gal11 activator-binding domain 1 has a four-helix fold with a small shallow hydrophobic cleft at its center. In the bound complex, eight residues of Gcn4 adopt a helical conformation, allowing three Gcn4 aromatic/aliphatic residues to insert into the Gal11 cleft. The protein-protein interface is dynamic and surprisingly simple, involving only hydrophobic interactions. This allows Gcn4 to bind Gal11 in multiple conformations and orientations, an example of a "fuzzy" complex, where the Gcn4-Gal11 interface cannot be described by a single conformation. Gcn4 uses a similar mechanism to bind two other unrelated activator-binding domains. Functional studies in yeast show the importance of residues at the protein interface, define the minimal requirements for a functional activator, and suggest a mechanism by which activators bind to multiple unrelated targets.