5N9J

Core Mediator of transcriptional regulation

Summary for 5N9J

• Entry DOI: 10.2210/pdb5n9j/pdb
• Descriptor: Mediator of RNA polymerase II transcription subunit 14, Mediator of RNA polymerase II transcription subunit 8, Mediator of RNA polymerase II transcription subunit 11, ... (15 entities in total)
• Functional Keywords: transcription, rna polymerase ii
• Biological source: Schizosaccharomyces pombe (Fission yeast); More
• Cellular location: Nucleus : Q9P7Y4 O94646 P87306 O14198 Q10317 O14010 Q9Y7N2 O94376 O60104 Q9Y821 Q9USH1 Q9US45; Cytoplasm : Q9P6Q0 P87310
• Total number of polymer chains: 15
• Total formula weight: 403415.40

Authors

Nozawa, K.,Schneider, T.R.,Cramer, P. (deposition date: 2017-02-25, release date: 2017-05-17, Last modification date: 2024-05-08)

Primary citation

Nozawa, K.,Schneider, T.R.,Cramer, P.
Core Mediator structure at 3.4 Angstrom extends model of transcription initiation complex.
Nature, 545:248-251, 2017

PubMed Abstract: Mediator is a multiprotein co-activator that binds the transcription pre-initiation complex (PIC) and regulates RNA polymerase (Pol) II. The Mediator head and middle modules form the essential core Mediator (cMed), whereas the tail and kinase modules play regulatory roles. The architecture of Mediator and its position on the PIC are known, but atomic details are limited to Mediator subcomplexes. Here we report the crystal structure of the 15-subunit cMed from Schizosaccharomyces pombe at 3.4 Å resolution. The structure shows an unaltered head module, and reveals the intricate middle module, which we show is globally required for transcription. Sites of known Mediator mutations cluster at the interface between the head and middle modules, and in terminal regions of the head subunits Med6 (ref. 16) and Med17 (ref. 17) that tether the middle module. The structure led to a model for Saccharomyces cerevisiae cMed that could be combined with the 3.6 Å cryo-electron microscopy structure of the core PIC (cPIC). The resulting atomic model of the cPIC-cMed complex informs on interactions of the submodules forming the middle module, called beam, knob, plank, connector, and hook. The hook is flexibly linked to Mediator by a conserved hinge and contacts the transcription initiation factor IIH (TFIIH) kinase that phosphorylates the carboxy (C)-terminal domain (CTD) of Pol II and was recently positioned on the PIC. The hook also contains residues that crosslink to the CTD and reside in a previously described cradle. These results provide a framework for understanding Mediator function, including its role in stimulating CTD phosphorylation by TFIIH.

PubMed: 28467824
DOI: 10.1038/nature22328

Experimental method

X-RAY DIFFRACTION (3.4 Å)