The iclR-type HTH domain is a DNA-binding, winged helix-turn-helix (wHTH) domain of about 60 amino acids present in transcription regulators of the iclR family, involved in carbon metabolism in eubacteria and archaea. The domains are named after Escherichia coli iclR (isocitrate lyase regulator), a repressor of the glyoxylate bypass operon for acetate utilization. Transcription regulators of the iclR family contain the DNA-binding wHTH domain in the N-terminal part. The C-terminal part contains a ~170 residues regulatory domain, termed Effector binding Domain (ED) as it may bind a small effector or signal molecule. Most iclR-type transcription regulators are repressors of specific catabolic genes in the absence of specific substrates, while excess of a specific effector triggers de-repression. IclR-like proteins can function as regulators for small catabolites and aromatic hydrocarbons metabolism, for control of sporulation and of virulence [1,2,3].

The structure of Thermotoga maritima iclR shows that the N-terminal DNA-binding domain is composed of three helices (H) and a β-hairpin (B1-B2) in the topology: H1-H2-H3-B1-B2 (see <PDB:1MKM>). The helix-turn-helix motif comprises helices 2 and 3; helix 3 is termed the recognition helix, like in other wHTHs where it binds the DNA major groove. The β-hairpin is called the wing. C-terminal to the DNA-binding domain, helix 4 and a short loop form a linking region. The C-terminal effector binding domain forms a structure similar to that of versatile, small molecule-binding GAF/PAS domains (see <PDB:1TF1>) [4]. IclR-like regulators can form dimers or tetramers and seem to recognize a short palindromic operator/promoter [2,3,4].

Some proteins known to contain an iclR-type HTH and effector binding domain:

• Escherichia coli iclR, a repressor of the aceBAK operon (also known as glyoxylate bypass operon) for acetate utilization.
• Streptomyces coelicolor gylR, a repressor of the gylCABX operon for the glycerol catabolism pathway. GylR functions glycerol-inducible, glucose-repressible, and also as a negative autoregulator.
• Erwinia chrysanthemi kdgR, a repressor of the genes involved in pectinolysis and in pectinase secretion.
• Escherichia coli mhpR, an activator of the mhpRABCDEF operon coding for components of the 3-hydroxyphenylpropionate degradation pathway.
• Acinetobacter strain ADP1 pcaU, a regulator of protocatechuate degradation. PcaU functions as a repressor or an activator depending on the levels of the inducer protocatechuate, and autoregulatory.
• Acinetobacter strain ADP1 pobR, a transcription activator of pobA, involved in the degradation of 4-hydroxybenzoate.

The profiles we developed span the entire DNA-binding iclR-type HTH domain and the effector binding domain, the latter including the linker region.