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The architecture of human general transcription factor TFIID core complex.

Authors :
Bieniossek C
Papai G
Schaffitzel C
Garzoni F
Chaillet M
Scheer E
Papadopoulos P
Tora L
Schultz P
Berger I
Source :
Nature [Nature] 2013 Jan 31; Vol. 493 (7434), pp. 699-702. Date of Electronic Publication: 2013 Jan 06.
Publication Year :
2013

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.

Details

Language :
English
ISSN :
1476-4687
Volume :
493
Issue :
7434
Database :
MEDLINE
Journal :
Nature
Publication Type :
Academic Journal
Accession number :
23292512
Full Text :
https://doi.org/10.1038/nature11791