Mediator structure and rearrangements required for holoenzyme formation
| Autor: | Kuang-Lei Tsai, Francisco J. Asturias, Ying Zhang, Joan W. Conaway, Laurence Florens, Ronald C. Conaway, Sneha Gopalan, Kenji Murakami, Michael P. Washburn, Xiaodi Yu, Ti-Chun Chao |
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| Rok vydání: | 2017 |
| Předmět: |
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Molecular 0301 basic medicine Protein Conformation Protein subunit RNA polymerase II Bioinformatics Article Structure-Activity Relationship 03 medical and health sciences Protein structure Mediator Transcription (biology) Schizosaccharomyces Binding Sites Mediator Complex Multidisciplinary General transcription factor biology Chemistry Cryoelectron Microscopy biology.organism_classification Cell biology Protein Subunits 030104 developmental biology Schizosaccharomyces pombe biology.protein RNA Polymerase II Schizosaccharomyces pombe Proteins Holoenzymes Protein Binding |
| Zdroj: | Nature. 544:196-201 |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/nature21393 |
| Popis: | The conserved Mediator co-activator complex has an essential role in the regulation of RNA polymerase II transcription in all eukaryotes. Understanding the structure and interactions of Mediator is crucial for determining how the complex influences transcription initiation and conveys regulatory information to the basal transcription machinery. Here we present a 4.4 A resolution cryo-electron microscopy map of Schizosaccharomyces pombe Mediator in which conserved Mediator subunits are individually resolved. The essential Med14 subunit works as a central backbone that connects the Mediator head, middle and tail modules. Comparison with a 7.8 A resolution cryo-electron microscopy map of a Mediator–RNA polymerase II holoenzyme reveals that changes in the structure of Med14 facilitate a large-scale Mediator rearrangement that is essential for holoenzyme formation. Our study suggests that access to different conformations and crosstalk between structural elements are essential for the Mediator regulation mechanism, and could explain the capacity of the complex to integrate multiple regulatory signals. Cryo-electron microscopy maps of the fission yeast Mediator complex and of a Mediator–RNA polymerase II holoenzyme reveal how changes in the Med14 subunit enable large-scale rearrangements of the Mediator structure that are essential for holoenzyme formation. The Mediator complex has an essential role in regulating RNA polymerase II transcription in eukaryotes. Here Francisco Asturias and colleagues use cryo-electron microscopy to obtain a near-atomic-resolution structure of the entire Mediator complex in fission yeast. They also determine the structure of the Mediator–RNA polymerase II holoenzyme. The Med14 subunit serves as a backbone to connect the head, middle and tail modules, and its flexibility enables the large-scale rearrangements that occur when the Mediator complex associates with RNA polymerase II. |
| Databáze: | OpenAIRE |
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