Chaperonin CCT checkpoint function in basal transcription factor TFIID assembly
Publication date
2018-12
Authors
Antonova, Simona V
Haffke, Matthias
Corradini, Eleonora
Mikuciunas, Mykolas
Low, Teck Y
Signor, Luca
van Es, Robert M.
Gupta, Kapil
Scheer, Elisabeth
Vos, Harmjan R.
Editors
Advisors
Supervisors
Document Type
Article
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taverne
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.
Keywords
Chaperonin Containing TCP-1/metabolism, Crystallography, X-Ray, HeLa Cells, Humans, Mass Spectrometry, Models, Molecular, Protein Domains, TATA-Binding Protein Associated Factors/chemistry, Transcription Factor TFIID/chemistry, Transcription, Genetic, Taverne, Journal Article, Research Support, Non-U.S. Gov't
Citation
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 & molecular biology, vol. 25, no. 12, pp. 1119-1127. https://doi.org/10.1038/s41594-018-0156-z