title: Crystal structure of the DNA-binding domain from Ndt80, a transcriptional activator required for meiosis in yeast.
abstract: Ndt80 is a transcriptional activator required for meiosis in the yeast Saccharomyces cerevisiae. Here, we report the crystal structure at 2.3 A resolution of the DNA-binding domain of Ndt80 experimentally phased by using the anomalous and isomorphous signal from a single ordered Se atom per molecule of 272-aa residues. The structure reveals a single approximately 32-kDa domain with a distinct fold comprising a beta-sandwich core elaborated with seven additional beta-sheets and three short alpha-helices. Inspired by the structure, we have performed a mutational analysis and defined a DNA-binding motif in this domain. The DNA-binding domain of Ndt80 is homologous to a number of proteins from higher eukaryotes, and the residues that we have shown are required for DNA binding by Ndt80 are highly conserved among this group of proteins. These results suggest that Ndt80 is the defining member of a previously uncharacterized family of transcription factors, including the human protein (C11orf9), which has been shown to be highly expressed in invasive or metastatic tumor cells.
authors.affiliation: Waksman Institute and Department of Chemistry and Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Sherwin P
authors.initials: SP
authors.lastname: Montano
authors.forename: Marie L
authors.initials: ML
authors.lastname: Coté
authors.forename: Ian
authors.initials: I
authors.lastname: Fingerman
authors.forename: Michael
authors.initials: M
authors.lastname: Pierce
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Vershon
authors.forename: Millie M
authors.initials: MM
authors.lastname: Georgiadis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D008540:Meiosis; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C097071:NDT80 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D004247:DNA