Journal: Science / Year: 2021 Title: Structures of the human Mediator and Mediator-bound preinitiation complex. Authors: Xizi Chen / Xiaotong Yin / Jiabei Li / Zihan Wu / Yilun Qi / Xinxin Wang / Weida Liu / Yanhui Xu / Abstract: The 1.3-megadalton transcription factor IID (TFIID) is required for preinitiation complex (PIC) assembly and RNA polymerase II (Pol II)-mediated transcription initiation on almost all genes. The 26- ...The 1.3-megadalton transcription factor IID (TFIID) is required for preinitiation complex (PIC) assembly and RNA polymerase II (Pol II)-mediated transcription initiation on almost all genes. The 26-subunit Mediator stimulates transcription and cyclin-dependent kinase 7 (CDK7)-mediated phosphorylation of the Pol II C-terminal domain (CTD). We determined the structures of human Mediator in the Tail module-extended (at near-atomic resolution) and Tail-bent conformations and structures of TFIID-based PIC-Mediator (76 polypeptides, ~4.1 megadaltons) in four distinct conformations. PIC-Mediator assembly induces concerted reorganization (Head-tilting and Middle-down) of Mediator and creates a Head-Middle sandwich, which stabilizes two CTD segments and brings CTD to CDK7 for phosphorylation; this suggests a CTD-gating mechanism favorable for phosphorylation. The TFIID-based PIC architecture modulates Mediator organization and TFIIH stabilization, underscoring the importance of TFIID in orchestrating PIC-Mediator assembly.
History
Deposition
Apr 16, 2021
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Header (metadata) release
May 19, 2021
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Map release
May 19, 2021
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Update
May 19, 2021
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Current status
May 19, 2021
Processing site: PDBj / Status: Released
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