Structures of the human Mediator and Mediator-bound preinitiation complex.
Cryoelectron Microscopy
Cyclin-Dependent Kinases
/ chemistry
DNA Helicases
/ chemistry
DNA-Binding Proteins
/ chemistry
Humans
Mediator Complex
/ chemistry
Mediator Complex Subunit 1
/ chemistry
Models, Molecular
Phosphorylation
Promoter Regions, Genetic
Protein Binding
Protein Conformation, alpha-Helical
Protein Domains
Protein Folding
Protein Structure, Quaternary
Protein Subunits
/ chemistry
RNA Polymerase II
/ chemistry
Transcription Factor TFIID
/ chemistry
Transcription Factor TFIIH
/ chemistry
Transcription Initiation, Genetic
Cyclin-Dependent Kinase-Activating Kinase
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
04 06 2021
04 06 2021
Historique:
received:
08
12
2020
revised:
15
03
2021
accepted:
27
04
2021
pubmed:
8
5
2021
medline:
22
6
2021
entrez:
7
5
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33958484
pii: science.abg0635
doi: 10.1126/science.abg0635
pii:
doi:
Substances chimiques
DNA-Binding Proteins
0
MED1 protein, human
0
MED14 protein, human
0
MED15 protein, human
0
Med17 protein, human
0
Mediator Complex
0
Mediator Complex Subunit 1
0
Protein Subunits
0
Transcription Factor TFIID
0
XPBC-ERCC-3 protein
146045-44-5
Transcription Factor TFIIH
148710-81-0
Cyclin-Dependent Kinases
EC 2.7.11.22
RNA Polymerase II
EC 2.7.7.-
DNA Helicases
EC 3.6.4.-
Cyclin-Dependent Kinase-Activating Kinase
EC 2.7.11.22
CDK7 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.