title: Zinc fingers, zinc clusters, and zinc twists in DNA-binding protein domains.
abstract: We now recognize three distinct motifs of DNA-binding zinc proteins: (i) zinc fingers, (ii) zinc clusters, and (iii) zinc twists. Until very recently, x-ray crystallographic or NMR three-dimensional structure analyses of DNA-binding zinc proteins have not been available to serve as standards of reference for the zinc binding sites of these families of proteins. Those of the DNA-binding domains of the fungal transcription factor GAL4 and the rat glucocorticoid receptor are the first to have been determined. Both proteins contain two zinc binding sites, and in both, cysteine residues are the sole zinc ligands. In GAL4, two zinc atoms are bound to six cysteine residues which form a "zinc cluster" akin to that of metallothionein; the distance between the two zinc atoms of GAL4 is approximately 3.5 A. In the glucocorticoid receptor, each zinc atom is bound to four cysteine residues; the interatomic zinc-zinc distance is approximately 13 A, and in this instance, a "zinc twist" is represented by a helical DNA recognition site located between the two zinc atoms. Zinc clusters and zinc twists are here recognized as two distinctive motifs in DNA-binding proteins containing multiple zinc atoms. For native "zinc fingers," structural data do not exist as yet; consequently, the interatomic distances between zinc atoms are not known. As further structural data become available, the structural and functional significance of these different motifs in their binding to DNA and other proteins participating in the transmission of the genetic message will become apparent.
authors.affiliation: Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115.
authors.forename: B L
authors.initials: BL
authors.lastname: Vallee
authors.forename: J E
authors.initials: JE
authors.lastname: Coleman
authors.forename: D S
authors.initials: DS
authors.lastname: Auld
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D011956:Receptors, Cell Surface; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D015032:Zinc