InterPro domain: IPR000843

The lacI-type HTH domain is a DNA-binding, helix-turn-helix (HTH) domain ofabout 50-60 residues present in the lacI/galR family of transcriptionalregulators involved in metabolic regulation in prokaryotes. Most of thesebacterial regulators recognize sugar-inducers. The family is named after theEscherichia coli lactose operon repressor lacI and galactose operon repressorgalR. LacI-type regulators are present in diverse bacterial genera, in thecytoplasm. The 'helix-turn-helix' DNA-binding motif is located in theN-terminal extremity of these transcriptional regulators. The C-terminal partof lacI-type regulators contains several regions that can be involved in (1)binding of inducers, which are sugars and their analogues and (2)oligomerization. The lac repressor is a tetramer, whilst the gal and cytrepressors are dimers. LacI-type transcriptional regulators are important inthe coordination of catabolic, metabolic and transport operons [ 1 , 2 ].

Several structures of lacI-type transcriptional regulators have been resolvedand their DNA-binding domain encompasses a headpiece, formed by a fold ofthree helices, followed by a hinge region, which can form a fourth alpha helixor hinge-helix. The helix-turn-helix motif comprises thefirst and second helices, the second being called the recognition helix. TheHTH is involved in DNA-binding into the major groove, while the hinge-helixfits into the minor groove and the complete domain specifically recognizes theoperator DNA [ 3 ].

Some proteins known to contain a lacI-type HTH domain:

• Bacillus subtilis ccpA and ccpB, transcriptional regulators involved in the catabolic repression of several operons.
• Salmonella typhimurium fruR, the fructose repressor, involved in the regulation of a large number of operons encoding enzymes which take part in central pathways of carbon metabolism.
• Escherichia coli lacI, the lactose operon repressor, serving as a model for gene regulation.
• Escherichia coli purF and purR, repressors involved in the regulation of enzymes for purine nucleotide synthesis.
• Haemophilus influenzae galR, a repressor of the galactose operon.

1. Sequence and evolution of the FruR protein of Salmonella typhimurium: a pleiotropic transcriptional regulatory protein possessing both activator and repressor functions which is homologous to the periplasmic ribose-binding protein. Res. Microbiol. 142, 951-63
2. A family of bacterial regulators homologous to Gal and Lac repressors. J. Biol. Chem. 267, 15869-74
3. Phylogenetic, structural and functional analyses of the LacI-GalR family of bacterial transcription factors. FEBS Lett. 377, 98-102