7enj

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Human Mediator (deletion of MED1-IDR) in a Tail-bent conformation (MED-B)Human Mediator (deletion of MED1-IDR) in a Tail-bent conformation (MED-B)

Structural highlights

7enj is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 4.4Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MED30_HUMAN Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.[1] [2]

Publication Abstract from PubMed

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.

Structures of the human Mediator and Mediator-bound preinitiation complex.,Chen X, Yin X, Li J, Wu Z, Qi Y, Wang X, Liu W, Xu Y Science. 2021 Jun 4;372(6546):eabg0635. doi: 10.1126/science.abg0635. Epub 2021 , May 6. PMID:33958484[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Baek HJ, Malik S, Qin J, Roeder RG. Requirement of TRAP/mediator for both activator-independent and activator-dependent transcription in conjunction with TFIID-associated TAF(II)s. Mol Cell Biol. 2002 Apr;22(8):2842-52. PMID:11909976 doi:10.1128/MCB.22.8.2842-2852.2002
  2. Baek HJ, Kang YK, Roeder RG. Human Mediator enhances basal transcription by facilitating recruitment of transcription factor IIB during preinitiation complex assembly. J Biol Chem. 2006 Jun 2;281(22):15172-81. Epub 2006 Apr 4. PMID:16595664 doi:M601983200
  3. 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. 2021 Jun 4;372(6546):eabg0635. PMID:33958484 doi:10.1126/science.abg0635

7enj, resolution 4.40Å

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OCA