Chaperonin CCT Checkpoint Function in Basal Transcription Factor TFIID Assembly

Simona V Antonova, Matthias Haffke, Eleanora 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

Research output: Contribution to journalArticle (Academic Journal)

9 Citations (Scopus)
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Abstract

TFIID is a cornerstone of eukaryotic gene regulation. Distinct TFIID complexes with unique subunit composition exist and several TFIID subunits are shared with other complexes, conveying intricate cellular decision making to control subunit allocation and functional assembly of this essential transcription factor. However, the underlying molecular mechanisms remain poorly understood. Here, we used 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 crucial for TFIID integrity, and for allocating TAF9 to TFIID or the 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 crafted in the cell, involving checkpoint decisions facilitated by a chaperone machine.
Original languageEnglish
Pages (from-to)1119-1127
Number of pages9
JournalNature Structural and Molecular Biology
Volume25
Issue number12
Early online date3 Dec 2018
DOIs
Publication statusPublished - Dec 2018

Structured keywords

  • Bristol BioDesign Institute
  • BrisSynBio

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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(12), 1119-1127. https://doi.org/10.1038/s41594-018-0156-z