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

Abstract

THE Cys2-His2 zinc-finger is the most widely occurring DNA-binding motif1–3. The first structure of a zinc-finger/DNA complex revealed a fairly simple mechanism for DNA recognition4 suggesting that the zinc-finger might represent a candidate template for designing proteins to recognize DNA5. Residues at three key positions in an α-helical 'reading head' play a dominant role in base-recognition and have been targets for mutagenesis experiments aimed at deriving a recognition code6–8. 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 experiments9,10. It is apparent from this structure that zinc-finger/ DNA recognition is more complex than was originally perceived.

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Fairall, L., Schwabe, J., Chapman, L. et al. The crystal structure of a two zinc-finger peptide reveals an extension to the rules for zinc-finger/DNA recognition. Nature 366, 483–487 (1993). https://doi.org/10.1038/366483a0

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