Mediator Structural Conservation and Implications for the Regulation Mechanism

Gang Cai, Tsuyoshi Imasaki, Yuichiro Takagi, Francisco J. Asturias

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Mediator, the multisubunit complex that plays an essential role in the regulation of transcription initiation in all eukaryotes, was isolated using an affinity purification protocol that yields pure material suitable for structural analysis. Conformational sorting of yeast Mediator single-particle images characterized the inherent flexibility of the complex and made possible calculation of a cryo-EM reconstruction. Comparison of free and RNA polymerase II (RNAPII) -associated yeast Mediator reconstructions demonstrates that intrinsic flexibility allows structural modules to reorganize and establish a complex network of contacts with RNAPII. We demonstrate that, despite very low sequence homology, the structures of human and yeast Mediators are surprisingly similar and the structural rearrangement that enables interaction of yeast Mediator with RNAPII parallels the structural rearrangement triggered by interaction of human Mediator with a nuclear receptor. This suggests that the topology and structural dynamics of Mediator constitute important elements of a conserved regulation mechanism.

Original languageEnglish (US)
Pages (from-to)559-567
Number of pages9
JournalStructure
Volume17
Issue number4
DOIs
StatePublished - Apr 15 2009

Fingerprint

RNA Polymerase II
Yeasts
Mediator Complex
Cytoplasmic and Nuclear Receptors
Sequence Homology
Eukaryota

Keywords

  • DNA
  • PROTEINS

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Mediator Structural Conservation and Implications for the Regulation Mechanism. / Cai, Gang; Imasaki, Tsuyoshi; Takagi, Yuichiro; Asturias, Francisco J.

In: Structure, Vol. 17, No. 4, 15.04.2009, p. 559-567.

Research output: Contribution to journalArticle

Cai, Gang ; Imasaki, Tsuyoshi ; Takagi, Yuichiro ; Asturias, Francisco J. / Mediator Structural Conservation and Implications for the Regulation Mechanism. In: Structure. 2009 ; Vol. 17, No. 4. pp. 559-567.
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