General transcription factor TFIID is a key component of RNA polymerase II transcription initiation. Human TFIID is a megadalton-sized complex comprising TATA-binding protein (TBP) and 13 TBP-associated factors (TAFs). TBP binds to core promoter DNA, recognizing the TATA-box. We identified a ternary complex formed by TBP and the histone fold (HF) domain-containing TFIID subunits TAF11 and TAF13. We demonstrate that TAF11/TAF13 competes for TBP binding with TATA-box DNA, and also with the N-terminal domain of TAF1 previously implicated in TATA-box mimicry. In an integrative approach combining crystal coordinates, biochemical analyses and data from cross-linking mass-spectrometry (CLMS), we determine the architecture of the TAF11/TAF13/TBP complex, revealing TAF11/TAF13 interaction with the DNA binding surface of TBP. We identify a highly conserved C-terminal TBP-interaction domain (CTID) in TAF13, which is essential for supporting cell growth. Our results thus have implications for cellular TFIID assembly and suggest a novel regulatory state for TFIID function.

BioCeV Faculty of Science Charles University Prague Czech Republic

BrisSynBio Centre The School of Biochemistry Faculty of Biomedical Sciences University of Bristol Bristol United Kingdom

Centre National de la Recherche Scientifique Illkirch France

Chair of Bioanalytics Institute of Biotechnology Technische Universität Berlin Berlin Germany

Department of Biochemistry University of Cambridge Cambridge United Kingdom

European Molecular Biology Laboratory Grenoble France

European Molecular Biology Laboratory Heidelberg Germany

Institut de Biologie Structurale IBS Grenoble France

Institut de Génétique et de Biologie Moléculaire et Cellulaire IGBMC Illkirch France

Institut National de la Santé et de la Recherche Médicale Illkirch France

Institute of Microbiology The Czech Academy of Sciences Vestec Czech Republic

Physical and Theoretical Chemistry Laboratory Oxford United Kingdom

Université de Strasbourg Illkirch France

Wellcome Trust Centre for Cell Biology University of Edinburgh Edinburgh United Kingdom

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