4.7 Article

Structural flexibility and functional interaction of mediator Cdk8 module

Journal

PROTEIN & CELL
Volume 4, Issue 12, Pages 911-920

Publisher

HIGHER EDUCATION PRESS
DOI: 10.1007/s13238-013-3069-y

Keywords

Mediator; Cdk8 kinase module; transcription regulation

Categories

Funding

  1. National Basic Research Program (973 Program) [2013CB910200]
  2. National Natural Science Foundation of China [31170694, 31222017]
  3. Ministry of Education of PRC [NCET-11-0874]
  4. Chinese Academy Of Sciences [48500108-6]

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Mediator is a highly conserved large protein complex (25 proteins, > 1000 kDa) and preeminently responsible for eukaryotic transcription, which contains a dissociable 'Cdk8 module'. Although increasing evidence demonstrates that Cdk8 module plays both positive and negative roles in transcription regulation, the detailed structure, and subunit organization, molecular mechanism how it regulates transcription remain elusive. Here we used single-particle electron microscopy to characterize the structure and subunit organization of the Cdk8 module and illuminated the substantial mobility of the Med13 subunit results in the structural flexibility. The Cdk8 module interaction with core Mediator is concurrent with active transcription in vivo. An interaction with the Cdk8 module induces core Mediator into very extended conformation in vitro, which is presumed to be an active functional state of Mediator. Taken together, our results illuminated the detailed architecture of Cdk8 module, and suggested the Cdk8 module could positively regulate transcription by modulating Mediator conformation.

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