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-Structure paper
タイトル | Structure of the human Mediator-RNA polymerase II pre-initiation complex. |
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ジャーナル・号・ページ | Nature, Vol. 594, Issue 7861, Page 129-133, Year 2021 |
掲載日 | 2021年4月26日 |
著者 | Srinivasan Rengachari / Sandra Schilbach / Shintaro Aibara / Christian Dienemann / Patrick Cramer / |
PubMed 要旨 | Mediator is a conserved coactivator complex that enables the regulated initiation of transcription at eukaryotic genes. Mediator is recruited by transcriptional activators and binds the pre- ...Mediator is a conserved coactivator complex that enables the regulated initiation of transcription at eukaryotic genes. Mediator is recruited by transcriptional activators and binds the pre-initiation complex (PIC) to stimulate the phosphorylation of RNA polymerase II (Pol II) and promoter escape. Here we prepare a recombinant version of human Mediator, reconstitute a 50-subunit Mediator-PIC complex and determine the structure of the complex by cryo-electron microscopy. The head module of Mediator contacts the stalk of Pol II and the general transcription factors TFIIB and TFIIE, resembling the Mediator-PIC interactions observed in the corresponding complex in yeast. The metazoan subunits MED27-MED30 associate with exposed regions in MED14 and MED17 to form the proximal part of the Mediator tail module that binds activators. Mediator positions the flexibly linked cyclin-dependent kinase (CDK)-activating kinase of the general transcription factor TFIIH near the linker to the C-terminal repeat domain of Pol II. The Mediator shoulder domain holds the CDK-activating kinase subunit CDK7, whereas the hook domain contacts a CDK7 element that flanks the kinase active site. The shoulder and hook domains reside in the Mediator head and middle modules, respectively, which can move relative to each other and may induce an active conformation of the CDK7 kinase to allosterically stimulate phosphorylation of the C-terminal domain. |
リンク | Nature / PubMed:33902108 |
手法 | EM (単粒子) |
解像度 | 4.0 Å |
構造データ | EMDB-12609: |
由来 |
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