Model of the Mediator middle module based on protein cross-linking
Laurent Larivière1, Clemens Plaschka, Martin Seizl
1Gene Center Munich and Department of Biochemistry, Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians-Universität München, Feodor-Lynen-Str. 25, 81377 Munich, Germany and Department of Biochemistry and Microbiology, Genome British Columbia Protein Centre, University of Victoria, No. 3101-4464 Markham Street, Vancouver Island Technology Park, Victoria, BC V8Z7X8, Canada.
Nucleic Acids Research
|August 14, 2013
Summary
Researchers developed a 3D model of the Mediator middle module, revealing its flexible, extended structure. This breakthrough aids understanding of transcription regulation by RNA polymerase II.
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- The Mediator complex is crucial for transcription regulation.
- It comprises distinct modules, including the head and middle modules.
- The structure of the Mediator middle module remains largely uncharacterized.
Purpose of the Study:
- To determine the three-dimensional structure of the Mediator middle module.
- To provide insights into the structural organization and flexibility of this essential transcription factor.
Main Methods:
- Integration of crystal structures and homology models.
- Utilized lysine-lysine cross-linking data obtained via mass spectrometry.
- Assembled a 6-subunit model of the Mediator middle module.
Main Results:
- A 3D model of the 6-subunit Mediator middle module was generated.
- The model features a central tetramer (Med4/Med9 and Med7/Med21 heterodimers) flanked by Med10 and Med31.
- The resulting structure is highly extended, indicating significant flexibility.
Conclusions:
- The determined structure provides a molecular basis for the Mediator middle module's function.
- The flexibility of the middle module is key to its role in RNA polymerase II regulation.
- This work facilitates future structure-function studies of transcription.
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