期刊
NATURE
卷 493, 期 7434, 页码 699-702出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature11791
关键词
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资金
- European Research Council (ERC)
- Agence Nationale de la Recherche (ANR)
- EC Marie Curie Action
- EC
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Centre National pour la Recherche Scientifique (CNRS)
- Association pour la Recherche sur le Cancer (ARC)
- Fondation pour la Recherche Medicale (FRM)
- ANR
- ChromAct
- TFIID-Complexes
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(1-3). TFIID is a megadalton-sized multiprotein complex composed of TATA-box-binding protein (TBP) and 13 TBP-associated factors (TAFs)(3). 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 TFIID4-6. A functional core-TFIID subcomplex was revealed in Drosophila nuclei, consisting of a subset of TAFs (TAF4, TAF5, TAF6, TAF9 and TAF12)(7). 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(8), conveying a transition from symmetry to asymmetry in the TFIID assembly pathway. Here we present the structure of human core-TFIID determined by cryoelectron microscopy at 11.6 angstrom 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.
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