page_title: Mediator (coactivator)
section_title: Structure
hierarchical_section_title: Mediator (coactivator) / Structure
caption_attribution_description: English: Mediator complex architecture with focus on Med 14
context_page_description: Mediator is a multiprotein complex that functions as a transcriptional coactivator in all eukaryotes. It was discovered in 1990 in the lab of Roger D. Kornberg, winner of the 2006 Nobel Prize in Chemistry. Mediator complexes interact with transcription factors and RNA polymerase II. The main function of mediator complexes is to transmit signals from the transcription factors to the polymerase.
  Mediator complexes are variable at the evolutionary, compositional and conformational levels. The first image shows only one "snapshot" of what a particular mediator complex might be composed of, but it certainly does not accurately depict the conformation of the complex in vivo. During evolution, mediator has become more complex. The yeast Saccharomyces cerevisiae is thought to have up to 21 subunits in the core mediator, while mammals have up to 26.
  Individual subunits can be absent or replaced by other subunits under different conditions. Also, there are many intrinsically disordered regions in mediator proteins, which may contribute to the conformational flexibility seen both with and without other bound proteins or protein complexes.
context_section_description: The yeast mediator complex is approximately as massive as a small subunit of a eukaryotic ribosome. The yeast mediator is composed of 25 subunits, while the mammalian mediator complexes are slightly larger. Mediator can be divided onto 4 main parts: The head, middle, tail, and the transiently associated CDK8 kinase module.
  Mediator subunits have many intrinsically disordered regions called "splies", which may be important to allow the structural changes of mediator that change the function of the complex. The figure shows how the splines of the Med 14 subunit connect a large portion of the complex together while still allowing flexibility.
  Mediator complexes that lack a subunit have been found or produced. These smaller mediators can still function normally in some activity, but lack other capability. This indicates somewhat independent function of some of the subunits while part of the larger complex.
  
  Another example of structural variability is seen in vertebrates, in which 3 paralogues of subunits of the cyclin-dependent kinase module have evolved by 3 independent gene duplication events followed by sequence divergence. 
  There is a report that mediator forms stable associations with a particular type of non-coding RNA, ncRNA-a. These stable associations have also been shown to regulate gene expression in vivo, and are prevented by mutations in MED12 that produce the human disease FG syndrome. Thus, the structure of a mediator complex can be augmented by RNA as well as proteinaceous transcription factors.
caption: Mediator complex architecture with focus on the disordered "spline" of Med 14[9]
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