Solution structure of the DNA binding domain from Dead ringer, a sequence‐specific AT‐rich interaction domain (ARID)

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.