THE CRYSTAL-STRUCTURE OF A 2 ZINC-FINGER PEPTIDE REVEALS AN EXTENSIONTO THE RULES FOR ZINC-FINGER DNA RECOGNITION

THE Cys2-His2 zinc-finger is the most widely occurring DNA-binding mot if1-3. The first structure of a zinc-finger/DNA complex revealed a fai rly simple mechanism for DNA recognition4 suggesting that the zinc-fin ger might represent a candidate template for designing proteins to rec ognize DNA-5. Residues at three key positions in an alpha-helical 'rea ding head' play a dominant role in base-recognition and have been targ ets for mutagenesis experiments aimed at deriving a recognition code6- 8. Here we report the structure of a two zinc-finger DNA-binding domai n from the protein Tramtrack complexed with DNA. The amino-terminal zi nc-finger and its interaction with DNA illustrate several novel featur es. 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-i nduced deformation of the DNA helix at a flexible A-T-A sequence and m ay give insight into previous mutagenesis experiments9,10. It is appar ent from this structure that zinc-finger/DNA recognition is more compl ex than was originally perceived.