The crystal structure of a two zinc-finger peptide reveals an extension to the rules for zinc-finger/DNA recognition

Nature. 1993 Dec 2;366(6454):483-7. doi: 10.1038/366483a0.

Abstract

The Cys2-His2 zinc-finger is the most widely occurring DNA-binding motif. The first structure of a zinc-finger/DNA complex revealed a fairly simple mechanism for DNA recognition suggesting that the zinc-finger might represent a candidate template for designing proteins to recognize DNA. Residues at three key positions in an alpha-helical 'reading head' play a dominant role in base-recognition and have been targets for mutagenesis experiments aimed at deriving a recognition code. Here we report the structure of a two zinc-finger DNA-binding domain from the protein Tramtrack complexed with DNA. The amino-terminal zinc-finger and its interaction with DNA illustrate several novel features. These include the use of a serine residue, which is semi-conserved and located outside the three key positions, to make a base contact. Its role in base-recognition correlates with a large, local, protein-induced deformation of the DNA helix at a flexible A-T-A sequence and may give insight into previous mutagenesis experiments. It is apparent from this structure that zinc-finger/DNA recognition is more complex than was originally perceived.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Crystallization
  • Crystallography, X-Ray
  • DNA / metabolism*
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Secondary
  • Repressor Proteins*
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism
  • Zinc Fingers*

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Repressor Proteins
  • Transcription Factors
  • ttk protein, Drosophila
  • DNA