Structure and dynamics of KH domains from FBP bound to single-stranded DNA

Nature. 2002 Feb 28;415(6875):1051-6. doi: 10.1038/4151051a.


Gene regulation can be tightly controlled by recognition of DNA deformations that are induced by stress generated during transcription. The KH domains of the FUSE-binding protein (FBP), a regulator of c-myc expression, bind in vivo and in vitro to the single-stranded far-upstream element (FUSE), 1,500 base pairs upstream from the c-myc promoter. FBP bound to FUSE acts through TFIIH at the promoter. Here we report the solution structure of a complex between the KH3 and KH4 domains of FBP and a 29-base single-stranded DNA from FUSE. The KH domains recognize two sites, 9-10 bases in length, separated by 5 bases, with KH4 bound to the 5' site and KH3 to the 3' site. The central portion of each site comprises a tetrad of sequence 5'd-ATTC for KH4 and 5'd-TTTT for KH3. Dynamics measurements show that the two KH domains bind as articulated modules to single-stranded DNA, providing a flexible framework with which to recognize transient, moving targets.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • DNA Helicases
  • DNA, Single-Stranded / chemistry
  • DNA, Single-Stranded / metabolism*
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation
  • Genes, myc
  • Humans
  • Hydrogen Bonding
  • Macromolecular Substances
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Protein Binding
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Tertiary
  • RNA-Binding Proteins


  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • FUBP1 protein, human
  • Macromolecular Substances
  • RNA-Binding Proteins
  • DNA Helicases

Associated data

  • PDB/1J4W