The solution structure of the Zalpha domain of the human RNA editing enzyme ADAR1 reveals a prepositioned binding surface for Z-DNA

Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12465-70. doi: 10.1073/pnas.96.22.12465.


Double-stranded RNA deaminase I (ADAR1) contains the Z-DNA binding domain Zalpha. Here we report the solution structure of free Zalpha and map the interaction surface with Z-DNA, confirming roles previously assigned to residues by mutagenesis. Comparison with the crystal structure of the (Zalpha)(2)/Z-DNA complex shows that most Z-DNA contacting residues in free Zalpha are prepositioned to bind Z-DNA, thus minimizing the entropic cost of binding. Comparison with homologous (alpha+beta)helix-turn-helix/B-DNA complexes suggests that binding of Zalpha to B-DNA is disfavored by steric hindrance, but does not eliminate the possibility that related domains may bind to both B- and Z-DNA.

Publication types

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

MeSH terms

  • Adenosine Deaminase / chemistry*
  • Adenosine Deaminase / metabolism*
  • Amino Acid Sequence
  • Binding Sites
  • DNA / metabolism*
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • RNA-Binding Proteins
  • Sequence Homology, Amino Acid
  • Solutions


  • DNA-Binding Proteins
  • RNA-Binding Proteins
  • Solutions
  • DNA
  • ADARB1 protein, human
  • Adenosine Deaminase

Associated data

  • PDB/1QGP