EM map of Human Mediator at 30 Å resolution (EMD-2635 [57]). Mediator Head, Middle and Tail modules are indicated. Individual panels display high-resolution structures of ((A), in green) the N-terminal domain of Human Med26 (PDB 5ODD [64]), ((B), in cyan) KIX domain of human Med15 (PDB 2GUT [80]), ((C), in yellow) ACID/PTOV domain of human Med25 (PDB 2L23, 2XNF, 2L6U and 2KY6 [73,75,76,79]) and ((D), in red) human Med23 (PDB 6H02 [72]). Med26 associates with the Middle domain via interactions with Med4, Med7 and Med19 [57]. Note that Med26 N- and C-terminal domains support interactions with TFIID and transcription elongation factors and with Mediator complex, respectively [65]. Med15 and Med23 have been assigned to the Tail module and Med25, which engages in an extensive network of interactions with other Tail subunits is believed to be a component of the Tail [57]. For details, refer to the text.