8TQC

Structure of the human CDK8 kinase module

8TQC の概要

• エントリーDOI: 10.2210/pdb8tqc/pdb
• EMDBエントリー: 41502
• 分子名称: Mediator of RNA polymerase II transcription subunit 12, Mediator of RNA polymerase II transcription subunit 13, Cyclin-dependent kinase 8, ... (5 entities in total)
• 機能のキーワード: transcription, mediator, cdk8, med12, med13, ckm.
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 569669.97

構造登録者

Chen, S.F.,Chao, T.C.,Kim, H.J.,Tang, H.C.,Khadka, S.,Li, T.,Murakami, K.,Boyer, T.G.,Tsai, K.L. (登録日: 2023-08-06, 公開日: 2024-10-09, 最終更新日: 2025-05-21)

主引用文献

Chao, T.C.,Chen, S.F.,Kim, H.J.,Tang, H.C.,Tseng, H.C.,Xu, A.,Palao 3rd, L.,Khadka, S.,Li, T.,Huang, M.F.,Lee, D.F.,Murakami, K.,Boyer, T.G.,Tsai, K.L.
Structural basis of the human transcriptional Mediator regulated by its dissociable kinase module.
Mol.Cell, 84:3932-3949.e10, 2024

PubMed Abstract: The eukaryotic transcriptional Mediator comprises a large core (cMED) and a dissociable CDK8 kinase module (CKM). cMED recruits RNA polymerase II (RNA Pol II) and promotes pre-initiation complex formation in a manner repressed by the CKM through mechanisms presently unknown. Herein, we report cryoelectron microscopy structures of the complete human Mediator and its CKM. The CKM binds to multiple regions on cMED through both MED12 and MED13, including a large intrinsically disordered region (IDR) in the latter. MED12 and MED13 together anchor the CKM to the cMED hook, positioning CDK8 downstream and proximal to the transcription start site. Notably, the MED13 IDR obstructs the recruitment of RNA Pol II/MED26 onto cMED by direct occlusion of their respective binding sites, leading to functional repression of cMED-dependent transcription. Combined with biochemical and functional analyses, these structures provide a conserved mechanistic framework to explain the basis for CKM-mediated repression of cMED function.

PubMed: 39321804
DOI: 10.1016/j.molcel.2024.09.001

実験手法

ELECTRON MICROSCOPY (3.8 Å)