6W1S

Atomic model of the mammalian Mediator complex

6W1S の概要

• エントリーDOI: 10.2210/pdb6w1s/pdb
• EMDBエントリー: 21514
• 分子名称: 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)
• 機能のキーワード: mouse mediator, complex, gene regulation
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 25
• 化学式量合計: 975066.81

構造登録者

Zhao, H.,Young, N.,Asturias, F. (登録日: 2020-03-04, 公開日: 2021-03-10, 最終更新日: 2024-10-23)

主引用文献

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

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: 31402173
DOI: 10.1016/j.cell.2019.07.011

実験手法

ELECTRON MICROSCOPY (4.02 Å)