Mediator is a multiprotein co-activator of RNA poly- merase (Pol) II transcription. Mediator contains a conserved core that comprises the ‘head’ and ‘middle’ modules. We present here a structure– function analysis of the essential Med11/22 hetero- dimer, a part of the head module. Med11/22 forms a conserved four-helix bundle domain with C-terminal extensions, which bind the central head subunit Med17. A highly conserved patch on the bundle surface is required for stable transcription pre- initiation complex formation on a Pol II promoter in vitro and in vivo and may recruit the general tran- scription factor TFIIH. The bundle domain fold is also present in the Mediator middle module sub- complex Med7/21 and is predicted in the Mediator heterodimers Med2/3, Med4/9, Med10/14 and Med28/30. The bundle domain thus represents a common building block that has been multiplied and functionally diversified during Mediator evolu- tion in eukaryotes.