title: Structure of a HAP1-DNA complex reveals dramatically asymmetric DNA binding by a homodimeric protein.
abstract: HAP1 is a member of a family of fungal transcription factors that contain a Zn2Cys6 binuclear cluster domain and bind as homodimers to sequences containing two DNA half sites. We have determined the 2.5 A crystal structure of HAP1 bound to a cognate upstream activation sequence from the CYC7 gene. The structure reveals that HAP1 is bound in a dramatically asymmetric manner to the DNA target. This asymmetry aligns the Zn2Cys6 domains in a tandem head-to-tail fashion to contact two DNA half sites, positions an N-terminal arm of one of the protein subunits to interact with the inter-half site base pairs in the DNA minor groove, and suggests a mechanism by which DNA-binding facilitates asymmetric dimerization by HAP1. Comparisons with the DNA complexes of the related GAL4, PPR1 and PUT3 proteins illustrate how a conserved protein domain can be reoriented to recognize DNA half sites of different polarities and how homodimeric proteins adopt dramatically asymmetric structures to recognize cognate DNA targets.
authors.affiliation: The Wistar Institute and The Department of Chemistry, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: King
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Guarente
authors.forename: R
authors.initials: R
authors.lastname: Marmorstein
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D019757:Carbon-Oxygen Lyases / Q000737:chemistry* / Q000378:metabolism; D004271:DNA, Fungal / Q000737:chemistry / Q000378:metabolism*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D019281:Dimerization; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae
chemical_list: D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D019757:Carbon-Oxygen Lyases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase