title: Mediator head subcomplex Med11/22 contains a common helix bundle building block with a specific function in transcription initiation complex stabilization.
abstract: Mediator is a multiprotein co-activator of RNA polymerase (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 heterodimer, 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 transcription factor TFIIH. The bundle domain fold is also present in the Mediator middle module subcomplex 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 evolution in eukaryotes.
authors.affiliation: Gene Center and Department of Biochemistry, Center for Integrated Protein Science Munich, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Seizl
authors.forename: Laurent
authors.initials: L
authors.lastname: Larivière
authors.forename: Toni
authors.initials: T
authors.lastname: Pfaffeneder
authors.forename: Larissa
authors.initials: L
authors.lastname: Wenzeck
authors.forename: Patrick
authors.initials: P
authors.lastname: Cramer
mesh_terms: D000595:Amino Acid Sequence; D056892:Mediator Complex / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry; D016415:Sequence Alignment; D014158:Transcription, Genetic
chemical_list: C531156:Med11 protein, S cerevisiae; D056892:Mediator Complex; C082148:SRB4 protein, S cerevisiae; C082150:SRB6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D012319:RNA Polymerase II