title: The architecture of human general transcription factor TFIID core complex.
abstract: The initiation of gene transcription by RNA polymerase II is regulated by a plethora of proteins in human cells. The first general transcription factor to bind gene promoters is transcription factor IID (TFIID). TFIID triggers pre-initiation complex formation, functions as a coactivator by interacting with transcriptional activators and reads epigenetic marks. TFIID is a megadalton-sized multiprotein complex composed of TATA-box-binding protein (TBP) and 13 TBP-associated factors (TAFs). Despite its crucial role, the detailed architecture and assembly mechanism of TFIID remain elusive. Histone fold domains are prevalent in TAFs, and histone-like tetramer and octamer structures have been proposed in TFIID. A functional core-TFIID subcomplex was revealed in Drosophila nuclei, consisting of a subset of TAFs (TAF4, TAF5, TAF6, TAF9 and TAF12). These core subunits are thought to be present in two copies in holo-TFIID, in contrast to TBP and other TAFs that are present in a single copy, conveying a transition from symmetry to asymmetry in the TFIID assembly pathway. Here we present the structure of human core-TFIID determined by cryo-electron microscopy at 11.6 Å resolution. Our structure reveals a two-fold symmetric, interlaced architecture, with pronounced protrusions, that accommodates all conserved structural features of the TAFs including the histone folds. We further demonstrate that binding of one TAF8-TAF10 complex breaks the original symmetry of core-TFIID. We propose that the resulting asymmetric structure serves as a functional scaffold to nucleate holo-TFIID assembly, by accreting one copy each of the remaining TAFs and TBP.
authors.affiliation: European Molecular Biology Laboratory Grenoble Outstation, Unit of Virus Host Cell Interactions UVHCI, UJF-CNRS-EMBL Unité Mixte International UMI 3265, 6 rue Jules Horowitz, 38042 Grenoble Cedex 9, France.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bieniossek
authors.forename: Gabor
authors.initials: G
authors.lastname: Papai
authors.forename: Christiane
authors.initials: C
authors.lastname: Schaffitzel
authors.forename: Frederic
authors.initials: F
authors.lastname: Garzoni
authors.forename: Maxime
authors.initials: M
authors.lastname: Chaillet
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Scheer
authors.forename: Petros
authors.initials: P
authors.lastname: Papadopoulos
authors.forename: Laszlo
authors.initials: L
authors.lastname: Tora
authors.forename: Patrick
authors.initials: P
authors.lastname: Schultz
authors.forename: Imre
authors.initials: I
authors.lastname: Berger
mesh_terms: D002478:Cells, Cultured; D020285:Cryoelectron Microscopy; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D035362:Transcription Factor TFIID / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D035362:Transcription Factor TFIID