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 α-helices and a short two-stranded anti-parallel β-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 α-helices; (ii) ARID proteins that supplement the core domain with an N-terminal α-helix; and (iii) extended-ARID proteins, which contain the core domain and additional α-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 β-hairpin and C-terminal α-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.
- AT-rich interaction domain
- DNA binding domain
- Dead ringer
ASJC Scopus subject areas
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)