Structure and mechanism of the Swi2/Snf2 remodeller Mot1 in complex with its substrate TBP

Nature. 2011 Jul 6;475(7356):403-7. doi: 10.1038/nature10215.


Swi2/Snf2-type ATPases regulate genome-associated processes such as transcription, replication and repair by catalysing the disruption, assembly or remodelling of nucleosomes or other protein-DNA complexes. It has been suggested that ATP-driven motor activity along DNA disrupts target protein-DNA interactions in the remodelling reaction. However, the complex and highly specific remodelling reactions are poorly understood, mostly because of a lack of high-resolution structural information about how remodellers bind to their substrate proteins. Mot1 (modifier of transcription 1 in Saccharomyces cerevisiae, denoted BTAF1 in humans) is a Swi2/Snf2 enzyme that specifically displaces the TATA box binding protein (TBP) from the promoter DNA and regulates transcription globally by generating a highly dynamic TBP pool in the cell. As a Swi2/Snf2 enzyme that functions as a single polypeptide and interacts with a relatively simple substrate, Mot1 offers an ideal system from which to gain a better understanding of this important enzyme family. To reveal how Mot1 specifically disrupts TBP-DNA complexes, we combined crystal and electron microscopy structures of Mot1-TBP from Encephalitozoon cuniculi with biochemical studies. Here we show that Mot1 wraps around TBP and seems to act like a bottle opener: a spring-like array of 16 HEAT (huntingtin, elongation factor 3, protein phosphatase 2A and lipid kinase TOR) repeats grips the DNA-distal side of TBP via loop insertions, and the Swi2/Snf2 domain binds to upstream DNA, positioned to weaken the TBP-DNA interaction by DNA translocation. A 'latch' subsequently blocks the DNA-binding groove of TBP, acting as a chaperone to prevent DNA re-association and ensure efficient promoter clearance. This work shows how a remodelling enzyme can combine both motor and chaperone activities to achieve functional specificity using a conserved Swi2/Snf2 translocase.

Publication types

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

MeSH terms

  • Binding Sites
  • Crystallization
  • Crystallography, X-Ray
  • DNA / chemistry
  • DNA / genetics
  • DNA / metabolism
  • DNA / ultrastructure
  • Encephalitozoon cuniculi / chemistry*
  • Fungal Proteins / chemistry*
  • Fungal Proteins / metabolism*
  • Fungal Proteins / ultrastructure
  • Microscopy, Electron
  • Models, Biological
  • Models, Molecular
  • Promoter Regions, Genetic / genetics
  • Protein Conformation
  • Protein Structure, Tertiary
  • Structure-Activity Relationship
  • Substrate Specificity
  • TATA-Box Binding Protein / chemistry*
  • TATA-Box Binding Protein / metabolism*
  • TATA-Box Binding Protein / ultrastructure
  • Transcription Factor TFIIB / chemistry
  • Transcription Factor TFIIB / metabolism


  • Fungal Proteins
  • TATA-Box Binding Protein
  • Transcription Factor TFIIB
  • DNA

Associated data

  • PDB/3OC3
  • PDB/3OCI