PROSITE documentation PDOC00366

LacI-type HTH domain signature and profile

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

Several structures of lacI-type transcriptional regulators have been resolved and their DNA-binding domain encompasses a headpiece, formed by a fold of three helices, followed by a hinge region, which can form a fourth α helix or hinge-helix (see <PDB:1L1M>). The helix-turn-helix motif comprises the first and second helices, the second being called the recognition helix. The HTH is involved in DNA-binding into the major groove, while the hinge-helix fits into the minor groove and the complete domain specifically recognizes the operator DNA [3,4].

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.

The pattern we developed spans the complete HTH motif, except for the last residue. We also developed a profile that covers the entire HTH and DNA-binding domain, including the hinge-helix and allows a more sensitive detection.