6W1S
Atomic model of the mammalian Mediator complex
Summary for 6W1S
| Entry DOI | 10.2210/pdb6w1s/pdb |
| EMDB information | 21514 |
| Descriptor | Mediator of RNA polymerase II transcription subunit 1, Mediator of RNA polymerase II transcription subunit 15, Mediator of RNA polymerase II transcription subunit 16, ... (25 entities in total) |
| Functional Keywords | mouse mediator, complex, gene regulation |
| Biological source | Mus musculus (Mouse) More |
| Total number of polymer chains | 25 |
| Total formula weight | 975066.81 |
| Authors | Zhao, H.,Young, N.,Asturias, F. (deposition date: 2020-03-04, release date: 2021-03-10, Last modification date: 2024-10-23) |
| Primary citation | El Khattabi, L.,Zhao, H.,Kalchschmidt, J.,Young, N.,Jung, S.,Van Blerkom, P.,Kieffer-Kwon, P.,Kieffer-Kwon, K.R.,Park, S.,Wang, X.,Krebs, J.,Tripathi, S.,Sakabe, N.,Sobreira, D.R.,Huang, S.C.,Rao, S.S.P.,Pruett, N.,Chauss, D.,Sadler, E.,Lopez, A.,Nobrega, M.A.,Aiden, E.L.,Asturias, F.J.,Casellas, R. A Pliable Mediator Acts as a Functional Rather Than an Architectural Bridge between Promoters and Enhancers. Cell, 178:1145-1158.e20, 2019 Cited by PubMed Abstract: While Mediator plays a key role in eukaryotic transcription, little is known about its mechanism of action. This study combines CRISPR-Cas9 genetic screens, degron assays, Hi-C, and cryoelectron microscopy (cryo-EM) to dissect the function and structure of mammalian Mediator (mMED). Deletion analyses in B, T, and embryonic stem cells (ESC) identified a core of essential subunits required for Pol II recruitment genome-wide. Conversely, loss of non-essential subunits mostly affects promoters linked to multiple enhancers. Contrary to current models, however, mMED and Pol II are dispensable to physically tether regulatory DNA, a topological activity requiring architectural proteins. Cryo-EM analysis revealed a conserved core, with non-essential subunits increasing structural complexity of the tail module, a primary transcription factor target. Changes in tail structure markedly increase Pol II and kinase module interactions. We propose that Mediator's structural pliability enables it to integrate and transmit regulatory signals and act as a functional, rather than an architectural bridge, between promoters and enhancers. PubMed: 31402173DOI: 10.1016/j.cell.2019.07.011 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.02 Å) |
Structure validation
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