This superfamily includes HetR, a DNA-binding serine-type protease required for heterocyst differentiation in the nitrogen-fixing cyanobacteria under conditions of nitrogen deprivation. The protein binds to a DNA palindrome upstream of hetP and other genes. The HetR monomer is composed of three distinct domains: the N-terminal domain which is involved in DNA binding, the middle domain designated the "flap", and a slightly smaller C-terminal domain designated the "hood". HetR forms a dimer upon DNA binding. That structure contains four distinct domains: an extended DNA-binding unit containing helix-turn-helix (HTH) motifs comprised of the two N-terminal sequences of the monomer; two histidine-rich flaps protruding on either side of the extended structure; and finally a hood comprised of the two C-terminal sequences. The whole HetR dimer becomes more symmetric in the presence of DNA. Overall, the flap orientations are adjusted to provide a more extended interaction with the twofold symmetric DNA duplex.

This entry describes the DNA-binding domain, located at the N-terminus, which contains HTH motifs that penetrate the major groove of the DNA. This part of the HetR surface is positively charged. The DNA-binding unit should obey twofold symmetry, consistent with the palindromic nature of the HetR recognition sequence identified experimentally. The size of the DNA-binding unit suggests that the DNA target is approximately 16-17 bp long. A cavity between the two HTH motifs is clearly large enough to accommodate the minor groove and phosphate units of DNA. The positively charged patch extends beyond the HTH motifs into the flap domains, so the DNA target interacting with HetR may be longer. The HetR DNA-binding surface shows some curvature, suggesting that the bound DNA target might be bent. Additionally, three nests were found in the DNA-binding domain (S31G32H33, H68H69L70, and L11G12P13). These nests are in close proximity to each other and two of them are on the interface between the DNA-binding unit and the flap domain.

PFAM:PF03574, INTERPRO:IPR005319,DOI:10.1073/pnas.1305971110,DOI:10.1073/pnas.1106840108