title: Solution structure of the DNA binding domain from Dead ringer, a sequence-specific AT-rich interaction domain (ARID).
abstract: The Dead ringer protein from Drosophila melanogaster is a transcriptional regulatory protein required for early embryonic development. It is the founding member of a large family of DNA binding proteins that interact with DNA through a highly conserved domain called the AT-rich interaction domain (ARID). The solution structure of the Dead ringer ARID (residues Gly262-Gly398) was determined using NMR spectroscopy. The ARID forms a unique globular structure consisting of eight alpha-helices and a short two-stranded anti-parallel beta-sheet. Amino acid sequence homology indicates that ARID DNA binding proteins are partitioned into three structural classes: (i) minimal ARID proteins that consist of a core domain formed by six alpha-helices; (ii) ARID proteins that supplement the core domain with an N-terminal alpha-helix; and (iii) extended-ARID proteins, which contain the core domain and additional alpha-helices at their N- and C-termini. Studies of the Dead ringer-DNA complex suggest that the major groove of DNA is recognized by a helix-turn-helix (HTH) motif and the adjacent minor grooves are contacted by a beta-hairpin and C-terminal alpha-helix. Primary homology suggests that all ARID-containing proteins contact DNA through the HTH and hairpin structures, but only extended-ARID proteins supplement this binding surface with a terminal helix.
authors.affiliation: Department of Chemistry and Biochemistry, Molecular Biology Institute and the UCLA-DOE Laboratory of Structural Biology and Genetics, University of California, Los Angeles, 405 Hilgard Avenue, Los Angeles, CA 90095-1570, USA.
authors.forename: J
authors.initials: J
authors.lastname: Iwahara
authors.forename: R T
authors.initials: RT
authors.lastname: Clubb
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000737:chemistry*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000378:metabolism*; D019077:Helix-Turn-Helix Motifs; D018398:Homeodomain Proteins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D017433:Protein Structure, Secondary; D016415:Sequence Alignment
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; C098342:Retn protein, Drosophila