Abstract
The Mediator complex transduces regulatory information from enhancers to promoters and performs essential roles in the initiation of transcription in eukaryotes. Human Mediator comprises 26 subunits forming three modules termed Head, Middle and Tail. Here we present the 2.8 Å crystal structure of MED23, the largest subunit from the human Tail module. The structure identifies 25 HEAT repeats-like motifs organized into 5 α-solenoids. MED23 adopts an arch-shaped conformation, with an N-terminal domain (Nter) protruding from a large core region. In the core four solenoids, motifs wrap on themselves, creating triangular-shaped structural motifs on both faces of the arch, with extended grooves propagating through the interfaces between the solenoid motifs. MED23 is known to interact with several specific transcription activators and is involved in splicing, elongation, and post-transcriptional events. The structure rationalizes previous biochemical observations and paves the way for improved understanding of the cross-talk between Mediator and transcriptional activators.
Highlights
The Mediator complex transduces regulatory information from enhancers to promoters and performs essential roles in the initiation of transcription in eukaryotes
In vitro and in vivo studies have demonstrated a specific interaction between MED23 and the ternary complex factor Ets-like protein[1] (ELK1), which is activated by MAPK signaling[4]
MED23 is composed of 25 HEAT repeats-like motifs organized into 5 α-solenoids and forming an arch-shaped conformation, with an N-terminal domain (Nter) protruding from a large core region
Summary
The Mediator complex transduces regulatory information from enhancers to promoters and performs essential roles in the initiation of transcription in eukaryotes. MED23 is composed of 25 HEAT repeats-like motifs organized into 5 α-solenoids and forming an arch-shaped conformation, with an N-terminal domain (Nter) protruding from a large core region. It is involved in the crystal packing, with its β-sheet stacking against helices H4, H6, and H8 from the N-HEAT solenoid domain of MED23.
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