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Nat Struct Mol Biol. 2018 Dec;25(12):1119-1127. doi: 10.1038/s41594-018-0156-z. Epub 2018 Dec 3.

Chaperonin CCT checkpoint function in basal transcription factor TFIID assembly.

Author information

1
Molecular Cancer Research and Regenerative Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
2
European Molecular Biology Laboratory (EMBL), Grenoble, France.
3
Chemical Biology and Therapeutics, Novartis Institutes for BioMedical Research, Basel, Switzerland.
4
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences and Netherlands Proteomics Centre, Utrecht University, Utrecht, The Netherlands.
5
UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
6
Université Grenoble Alpes, CEA, CNRS, IBS (Institut de Biologie Structurale), Grenoble, France.
7
Molecular Cancer Research, Center for Molecular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
8
Bristol Synthetic Biology Centre BrisSynBio, Biomedical Sciences, School of Biochemistry, University of Bristol, Bristol, UK.
9
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.
10
Centre National de la Recherche Scientifique, UMR 7104, Illkirch, France.
11
Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France.
12
Université de Strasbourg, Illkirch, France.
13
Molecular Cancer Research and Regenerative Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands. m.timmers@dkfz-heidelberg.de.
14
Department of Urology, Medical Center-University of Freiburg, Freiburg, Germany. m.timmers@dkfz-heidelberg.de.
15
Deutsches Konsortium für Translationale Krebsforschung (DKTK), Standort Freiburg, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany. m.timmers@dkfz-heidelberg.de.
16
Bristol Synthetic Biology Centre BrisSynBio, Biomedical Sciences, School of Biochemistry, University of Bristol, Bristol, UK. imre.berger@bristol.ac.uk.

Abstract

TFIID is a cornerstone of eukaryotic gene regulation. Distinct TFIID complexes with unique subunit compositions exist and several TFIID subunits are shared with other complexes, thereby conveying precise cellular control of subunit allocation and functional assembly of this essential transcription factor. However, the molecular mechanisms that underlie the regulation of TFIID remain poorly understood. Here we use quantitative proteomics to examine TFIID submodules and assembly mechanisms in human cells. Structural and mutational analysis of the cytoplasmic TAF5-TAF6-TAF9 submodule identified novel interactions that are crucial for TFIID integrity and for allocation of TAF9 to TFIID or the Spt-Ada-Gcn5 acetyltransferase (SAGA) co-activator complex. We discover a key checkpoint function for the chaperonin CCT, which specifically associates with nascent TAF5 for subsequent handover to TAF6-TAF9 and ultimate holo-TFIID formation. Our findings illustrate at the molecular level how multisubunit complexes are generated within the cell via mechanisms that involve checkpoint decisions facilitated by a chaperone.

PMID:
30510221
PMCID:
PMC6292499
DOI:
10.1038/s41594-018-0156-z
[Indexed for MEDLINE]
Free PMC Article

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