Structural highlights
Function
MED15_YEAST Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. The Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins. It has an important role in the negative regulation of Ty transcription.[1] [2] [3]
Publication Abstract from PubMed
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.
The acidic transcription activator Gcn4 binds the mediator subunit Gal11/Med15 using a simple protein interface forming a fuzzy complex.,Brzovic PS, Heikaus CC, Kisselev L, Vernon R, Herbig E, Pacheco D, Warfield L, Littlefield P, Baker D, Klevit RE, Hahn S Mol Cell. 2011 Dec 23;44(6):942-53. PMID:22195967[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nair D, Kim Y, Myers LC. Mediator and TFIIH govern carboxyl-terminal domain-dependent transcription in yeast extracts. J Biol Chem. 2005 Oct 7;280(40):33739-48. Epub 2005 Aug 2. PMID:16076843 doi:http://dx.doi.org/M506067200
- ↑ van de Peppel J, Kettelarij N, van Bakel H, Kockelkorn TT, van Leenen D, Holstege FC. Mediator expression profiling epistasis reveals a signal transduction pathway with antagonistic submodules and highly specific downstream targets. Mol Cell. 2005 Aug 19;19(4):511-22. PMID:16109375 doi:http://dx.doi.org/10.1016/j.molcel.2005.06.033
- ↑ Takagi Y, Kornberg RD. Mediator as a general transcription factor. J Biol Chem. 2006 Jan 6;281(1):80-9. Epub 2005 Nov 1. PMID:16263706 doi:http://dx.doi.org/M508253200
- ↑ Brzovic PS, Heikaus CC, Kisselev L, Vernon R, Herbig E, Pacheco D, Warfield L, Littlefield P, Baker D, Klevit RE, Hahn S. The acidic transcription activator Gcn4 binds the mediator subunit Gal11/Med15 using a simple protein interface forming a fuzzy complex. Mol Cell. 2011 Dec 23;44(6):942-53. PMID:22195967 doi:http://dx.doi.org/10.1016/j.molcel.2011.11.008
