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TitleStructures of the human Mediator and Mediator-bound preinitiation complex.
Journal, issue, pagesScience, Vol. 372, Issue 6546, Year 2021
Publish dateMay 6, 2021
AuthorsXizi Chen / Xiaotong Yin / Jiabei Li / Zihan Wu / Yilun Qi / Xinxin Wang / Weida Liu / Yanhui Xu /
PubMed AbstractThe 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.
External linksScience / PubMed:33958484
MethodsEM (single particle)
Resolution2.8 - 7.1 Å
Structure data

EMDB-31191, PDB-7emf:
Human Mediator (deletion of MED1-IDR) in a Tail-extended conformation
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-31192:
Human Mediator (deletion of MED1-IDR) Head module
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-31193:
Human Mediator (deletion of MED1-IDR) Middle module
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-31194:
Human Mediator (deletion of MED1-IDR) Tail module
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-31195:
Structure of the human Mediator MED1 module
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-31196:
Human Mediator (deletion of MED1-IDR) Head module near MED6
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-31204, PDB-7ena:
TFIID-based PIC-Mediator holo-complex in pre-assembled state (pre-hPIC-MED)
Method: EM (single particle) / Resolution: 4.07 Å

EMDB-31205:
TFIID-based PIC-MED holo-complex (deletion of MED1-IDR) in an intermediate state (state2)
Method: EM (single particle) / Resolution: 4 Å

EMDB-31206:
TFIID-based PIC-MED holo-complex (deletion of MED1-IDR) in an intermediate state (state3)
Method: EM (single particle) / Resolution: 5.22 Å

EMDB-31207, PDB-7enc:
TFIID-based PIC-Mediator holo-complex in fully-assembled state (hPIC-MED)
Method: EM (single particle) / Resolution: 4.13 Å

EMDB-31211, PDB-7enj:
Human Mediator (deletion of MED1-IDR) in a Tail-bent conformation (MED-B)
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-31212:
Human Mediator (deletion of MED1-IDR) Tail module in a bent conformation
Method: EM (single particle) / Resolution: 4.5 Å

EMDB-31213:
Human Mediator in a Tail-bent conformation (MED-B)
Method: EM (single particle) / Resolution: 7.1 Å

EMDB-31214:
Human Mediator in a Tail-extended conformation (MED-E)
Method: EM (single particle) / Resolution: 4 Å

EMDB-31215:
TFIID-based PIC-MED holo-complex
Method: EM (single particle) / Resolution: 6.5 Å

Chemicals

ChemComp-ZN:
ZINC ION / Zinc

ChemComp-MG:
MAGNESIUM ION / Magnesium

ChemComp-SF4:
IRON/SULFUR CLUSTER / Iron–sulfur cluster

Source
  • homo sapiens (human)
  • sus scrofa (pig)
  • Pig (pig)
KeywordsTRANSCRIPTION / Mediator complex / mediator / preinitiation complex / transcription initiation

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