title: 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 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.
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: L
authors.initials: L
authors.lastname: Fairall
authors.forename: J W
authors.initials: JW
authors.lastname: Schwabe
authors.forename: L
authors.initials: L
authors.lastname: Chapman
authors.forename: J T
authors.initials: JT
authors.lastname: Finch
authors.forename: D
authors.initials: D
authors.lastname: Rhodes
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003460:Crystallization; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D029721:Drosophila Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D012097:Repressor Proteins; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C075878:ttk protein, Drosophila; D004247:DNA