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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cross-Linking Reagents / chemistry
  • Cryoelectron Microscopy
  • DNA / chemistry
  • DNA / metabolism
  • Humans
  • Promoter Regions, Genetic*
  • Protein Binding
  • Protein Domains
  • Protein Multimerization
  • Protein Stability
  • TATA-Box Binding Protein / chemistry*
  • Transcription Factor TFIID / chemistry*
  • Transcription Initiation, Genetic*

Substances

  • Cross-Linking Reagents
  • TATA-Box Binding Protein
  • TBP protein, human
  • Transcription Factor TFIID
  • DNA