7ENA

TFIID-based PIC-Mediator holo-complex in pre-assembled state (pre-hPIC-MED)

This is a non-PDB format compatible entry.

Summary for 7ENA

• Entry DOI: 10.2210/pdb7ena/pdb
• EMDB information: 31204
• Descriptor: CDK-activating kinase assembly factor MAT1, RPB1, DNA-directed RNA polymerase subunit beta, ... (73 entities in total)
• Functional Keywords: mediator, preinitiation complex, transcription initiation, transcription
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 76
• Total formula weight: 3882078.91

Authors

Chen, X.,Qi, Y.,Wang, X.,Wu, Z.,Yin, X.,Li, J.,Liu, W.,Xu, Y. (deposition date: 2021-04-16, release date: 2021-05-26, Last modification date: 2024-11-13)

Primary citation

Chen, X.,Yin, X.,Li, J.,Wu, Z.,Qi, Y.,Wang, X.,Liu, W.,Xu, Y.
Structures of the human Mediator and Mediator-bound preinitiation complex.
Science, 372:-, 2021

PubMed 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-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.

PubMed: 33958484
DOI: 10.1126/science.abg0635

Experimental method

ELECTRON MICROSCOPY (4.07 Å)