8T1L

Atomic model of the mammalian mouse Mediator complex with CKM module

Summary for 8T1L

• Entry DOI: 10.2210/pdb8t1l/pdb
• EMDB information: 40971
• Descriptor: Mediator of RNA polymerase II transcription subunit 8, Mediator of RNA polymerase II transcription subunit 15, Mediator of RNA polymerase II transcription subunit 16, ... (26 entities in total)
• Functional Keywords: mouse mediator, gene regulation, ckm module
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 26
• Total formula weight: 1520953.12

Authors

Zhao, H.,Asturias, F. (deposition date: 2023-06-02, release date: 2024-07-03, Last modification date: 2025-01-15)

Primary citation

Zhao, H.,Li, J.,Xiang, Y.,Malik, S.,Vartak, S.V.,Veronezi, G.M.B.,Young, N.,Riney, M.,Kalchschmidt, J.,Conte, A.,Jung, S.K.,Ramachandran, S.,Roeder, R.G.,Shi, Y.,Casellas, R.,Asturias, F.J.
An IDR-dependent mechanism for nuclear receptor control of Mediator interaction with RNA polymerase II.
Mol.Cell, 84:2648-2664.e10, 2024

PubMed Abstract: The essential Mediator (MED) coactivator complex plays a well-understood role in regulation of basal transcription in all eukaryotes, but the mechanism underlying its role in activator-dependent transcription remains unknown. We investigated modulation of metazoan MED interaction with RNA polymerase II (RNA Pol II) by antagonistic effects of the MED26 subunit and the CDK8 kinase module (CKM). Biochemical analysis of CKM-MED showed that the CKM blocks binding of the RNA Pol II carboxy-terminal domain (CTD), preventing RNA Pol II interaction. This restriction is eliminated by nuclear receptor (NR) binding to CKM-MED, which enables CTD binding in a MED26-dependent manner. Cryoelectron microscopy (cryo-EM) and crosslinking-mass spectrometry (XL-MS) revealed that the structural basis for modulation of CTD interaction with MED relates to a large intrinsically disordered region (IDR) in CKM subunit MED13 that blocks MED26 and CTD interaction with MED but is repositioned upon NR binding. Hence, NRs can control transcription initiation by priming CKM-MED for MED26-dependent RNA Pol II interaction.

PubMed: 38955181
DOI: 10.1016/j.molcel.2024.06.006

Experimental method

ELECTRON MICROSCOPY (4.83 Å)