The architecture of human general transcription factor TFIID core complex

Christoph Bieniossek, Gabor Papai, Christiane Schaffitzel, Frederic Garzoni, Maxime Chaillet, Elisabeth Scheer, Petros Papadopoulos, Laszlo Tora, Patrick Schultz, Imre Berger

Research output: Contribution to journalArticle (Academic Journal)peer-review

104 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)699-702
Number of pages4
JournalNature
Volume493
Issue number7434
DOIs
Publication statusPublished - 31 Jan 2013

Keywords

  • Cells, Cultured
  • Cryoelectron Microscopy
  • HeLa Cells
  • Humans
  • Models, Molecular
  • Protein Binding
  • Protein Structure, Tertiary
  • Transcription Factor TFIID

Fingerprint

Dive into the research topics of 'The architecture of human general transcription factor TFIID core complex'. Together they form a unique fingerprint.

Cite this