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Science. 2018 Dec 21;362(6421). pii: eaau8872. doi: 10.1126/science.aau8872. Epub 2018 Nov 15.

Structure of human TFIID and mechanism of TBP loading onto promoter DNA.

Author information

1
Biophysics Graduate Group, University of California, Berkeley, CA 94720, USA.
2
Molecular Biophysics and Integrative Bio-Imaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
3
California Institute for Quantitative Biology (QB3), University of California, Berkeley, CA 94720, USA.
4
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
5
Institute for Systems Biology, Seattle, WA 98109, USA.
6
Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.
7
Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA.
8
Biophysics Graduate Group, University of California, Berkeley, CA 94720, USA. enogales@lbl.gov.
9
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.

Abstract

The general transcription factor IID (TFIID) is a critical component of the eukaryotic transcription preinitiation complex (PIC) and is responsible for recognizing the core promoter DNA and initiating PIC assembly. We used cryo-electron microscopy, chemical cross-linking mass spectrometry, and biochemical reconstitution to determine the complete molecular architecture of TFIID and define the conformational landscape of TFIID in the process of TATA box-binding protein (TBP) loading onto promoter DNA. Our structural analysis revealed five structural states of TFIID in the presence of TFIIA and promoter DNA, showing that the initial binding of TFIID to the downstream promoter positions the upstream DNA and facilitates scanning of TBP for a TATA box and the subsequent engagement of the promoter. Our findings provide a mechanistic model for the specific loading of TBP by TFIID onto the promoter.

PMID:
30442764
DOI:
10.1126/science.aau8872

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