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 into 4 main parts: The head, middle, tail, and the transiently associated CDK8 kinase module.
Mediator subunits have many intrinsically disordered regions called "splines", which may be important to allow the structural changes of the 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 capabilities. This indicates a somewhat independent function of some of the subunits while being 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.