Mediator structure and rearrangements required for holoenzyme formation

Nature. 2017 Apr 13;544(7649):196-201. doi: 10.1038/nature21393. Epub 2017 Mar 1.


The conserved Mediator co-activator complex has an essential role in the regulation of RNA polymerase II transcription in all eukaryotes. Understanding the structure and interactions of Mediator is crucial for determining how the complex influences transcription initiation and conveys regulatory information to the basal transcription machinery. Here we present a 4.4 Å resolution cryo-electron microscopy map of Schizosaccharomyces pombe Mediator in which conserved Mediator subunits are individually resolved. The essential Med14 subunit works as a central backbone that connects the Mediator head, middle and tail modules. Comparison with a 7.8 Å resolution cryo-electron microscopy map of a Mediator-RNA polymerase II holoenzyme reveals that changes in the structure of Med14 facilitate a large-scale Mediator rearrangement that is essential for holoenzyme formation. Our study suggests that access to different conformations and crosstalk between structural elements are essential for the Mediator regulation mechanism, and could explain the capacity of the complex to integrate multiple regulatory signals.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cryoelectron Microscopy
  • Holoenzymes / chemistry
  • Holoenzymes / metabolism
  • Holoenzymes / ultrastructure
  • Mediator Complex / chemistry*
  • Mediator Complex / metabolism*
  • Mediator Complex / ultrastructure
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • RNA Polymerase II / chemistry*
  • RNA Polymerase II / metabolism
  • RNA Polymerase II / ultrastructure*
  • Schizosaccharomyces
  • Schizosaccharomyces pombe Proteins / chemistry
  • Schizosaccharomyces pombe Proteins / metabolism
  • Schizosaccharomyces pombe Proteins / ultrastructure
  • Structure-Activity Relationship


  • Holoenzymes
  • Med14 protein, S pombe
  • Mediator Complex
  • Protein Subunits
  • Schizosaccharomyces pombe Proteins
  • RNA Polymerase II