High-resolution structures of variant Zif268-DNA complexes: implications for understanding zinc finger-DNA recognition

Structure. 1998 Apr 15;6(4):451-64. doi: 10.1016/s0969-2126(98)00047-1.


Background: Zinc fingers of the Cys2-His2 class comprise one of the largest families of eukaryotic DNA-binding motifs and recognize a diverse set of DNA sequences. These proteins have a relatively simple modular structure and key base contacts are typically made by a few residues from each finger. These features make the zinc finger motif an attractive system for designing novel DNA-binding proteins and for exploring fundamental principles of protein-DNA recognition.

Results: Here we report the X-ray crystal structures of zinc finger-DNA complexes involving three variants of Zif268, with multiple changes in the recognition helix of finger one. We describe the structure of each of these three-finger peptides bound to its corresponding target site. To help elucidate the differential basis for site-specific recognition, the structures of four other complexes containing various combinations of these peptides with alternative binding sites have also been determined.

Conclusions: The protein-DNA contacts observed in these complexes reveal the basis for the specificity demonstrated by these Zif268 variants. Many, but not all, of the contacts can be rationalized in terms of a recognition code, but the predictive value of such a code is limited. The structures illustrate how modest changes in the docking arrangement accommodate the new sidechain-base and sidechain-phosphate interactions. Such adaptations help explain the versatility of naturally occurring zinc finger proteins and their utility in design.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Binding Sites / physiology
  • Crystallography, X-Ray
  • DNA-Binding Proteins / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Oligodeoxyribonucleotides / chemistry*
  • Peptide Fragments / chemistry
  • Protein Conformation
  • Protein Structure, Secondary
  • Transcription Factors / chemistry*
  • Water / chemistry
  • Zinc Fingers / physiology*


  • DNA-Binding Proteins
  • Oligodeoxyribonucleotides
  • Peptide Fragments
  • Transcription Factors
  • Water