Chaperonin CCT checkpoint function in basal transcription factor TFIID assembly

Simona V Antonova; Matthias Haffke; Eleonora Corradini; Mykolas Mikuciunas; Teck Y Low; Luca Signor; Robert M van Es; Kapil Gupta; Elisabeth Scheer; Harmjan R Vos; László Tora; Albert J R Heck; H T Marc Timmers; Imre Berger

doi:10.1038/s41594-018-0156-z

Chaperonin CCT checkpoint function in basal transcription factor TFIID assembly

Simona V Antonova, Matthias Haffke, Eleonora Corradini, Mykolas Mikuciunas, Teck Y Low, Luca Signor, Robert M van Es, Kapil Gupta, Elisabeth Scheer, Harmjan R Vos, László Tora, Albert J R Heck, H T Marc Timmers, Imre Berger

University Medical Center Utrecht
Chemical Biology and Therapeutics, Novartis Institutes for BioMedical Research, Basel, Switzerland.
UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Université Grenoble Alpes, CEA, CNRS, IBS (Institut de Biologie Structurale), Grenoble, France.
Bristol Synthetic Biology Centre BrisSynBio, Biomedical Sciences, School of Biochemistry, University of Bristol, Bristol, UK.
Université de Strasbourg, Illkirch, France.
Deutsches Konsortium für Translationale Krebsforschung (DKTK), Standort Freiburg, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany. [email protected].
Bristol Synthetic Biology Centre BrisSynBio, Biomedical Sciences, School of Biochemistry, University of Bristol, Bristol, UK. [email protected].

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	1119-1127
Journal	Nature Structural and Molecular Biology
Volume	25
DOIs	https://doi.org/10.1038/s41594-018-0156-z
Publication status	Published - 3 Dec 2018

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antonovaFinal published version, 3.96 MBLicence: Taverne

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Antonova, S. V., Haffke, M., Corradini, E., Mikuciunas, M., Low, T. Y., Signor, L., van Es, R. M., Gupta, K., Scheer, E., Vos, H. R., Tora, L., Heck, A. J. R., Timmers, H. T. M., & Berger, I. (2018). Chaperonin CCT checkpoint function in basal transcription factor TFIID assembly. Nature Structural and Molecular Biology, 25, 1119-1127. https://doi.org/10.1038/s41594-018-0156-z

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title = "Chaperonin CCT checkpoint function in basal transcription factor TFIID assembly",

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.",

author = "Antonova, {Simona V} and Matthias Haffke and Eleonora Corradini and Mykolas Mikuciunas and Low, {Teck Y} and Luca Signor and {van Es}, {Robert M} and Kapil Gupta and Elisabeth Scheer and Vos, {Harmjan R} and L{\'a}szl{\'o} Tora and Heck, {Albert J R} and Timmers, {H T Marc} and Imre Berger",

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month = dec,

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doi = "10.1038/s41594-018-0156-z",

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AU - Antonova, Simona V

AU - Haffke, Matthias

AU - Corradini, Eleonora

AU - Mikuciunas, Mykolas

AU - Low, Teck Y

AU - Signor, Luca

AU - van Es, Robert M

AU - Gupta, Kapil

AU - Scheer, Elisabeth

AU - Vos, Harmjan R

AU - Tora, László

AU - Heck, Albert J R

AU - Timmers, H T Marc

AU - Berger, Imre

PY - 2018/12/3

Y1 - 2018/12/3

N2 - 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.

AB - 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.

U2 - 10.1038/s41594-018-0156-z

DO - 10.1038/s41594-018-0156-z

M3 - Article

C2 - 30510221

SN - 1545-9993

VL - 25

SP - 1119

EP - 1127

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

ER -

Chaperonin CCT checkpoint function in basal transcription factor TFIID assembly

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