The crp-type HTH domain is a DNA-binding, winged helix-turn-helix (wHTH) domain of about 70-75 amino acids present in transcription regulators of the crp-fnr family, involved in the control of virulence factors, enzymes of aromatic ring degradation, nitrogen fixation, photosynthesis, and various types of respiration. The crp-fnr family is named after the first members identified in E.coli: the well characterized cyclic AMP receptor protein CRP or CAP (catabolite activator protein) and the fumarate and nitrate reductase regulator Fnr. crp-type HTH domain proteins occur in most bacteria and in chloroplasts of red algae. The DNA-binding HTH domain is located in the C-terminal part; the N-terminal part of the proteins of the crp-fnr family contains a nucleotide-binding domain (see <PDOC00691>) and a dimerization/linker helix occurs in between. The crp-fnr regulators predominantly act as transcription activators, but can also be important repressors, and respond to diverse intracellular and exogenous signals, such as cAMP, anoxia, redox state, oxidative and nitrosative stress, carbon monoxide, nitric oxide or temperature [1,2].

The structure of the crp-type DNA-binding domain (see <PDB:1LB2>) shows that the helices (H) forming the helix-turn-helix motif (H2-H3) are flanked by two β-hairpin (B) wings, in the topology H1-B1-B2-H2-H3-B3-B4. Helix 3 is termed the recognition helix, as in most wHTHs it binds the DNA major groove [3,4,5].

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

• Escherichia coli crp (also known as cAMP receptor), a protein that complexes with cAMP and regulates the transcription of several catabolite-sensitive operons.
• Escherichia coli fnr, a protein that activates genes for proteins involved in a variety of anaerobic electron transport systems.
• Rhizobium leguminosarum fnrN, a transcription regulator of nitrogen fixation.
• Rhodobacter sphaeroides fnrL, a transcription activator of genes for heme biosynthesis, bacteriochlorophyll synthesis and the light-harvesting complex LHII.
• Rhizobiacae fixK, a protein that regulates nitrogen fixation genes, both positively and negatively.
• Lactobacillus casei fnr-like protein flp, a putative regulatory protein linked to the trpDCFBA operon.
• Cyanobacteria ntcA, a regulator of the expression of genes subject to nitrogen control.
• Xanthomonas campestris clp, a protein involved in the regulation of phytopathogenicity. Clp controls the production of extracellular enzymes, xanthan gum and pigment, either positively or negatively.

The 'helix-turn-helix' DNA-binding motif of these proteins is located in the C-terminal part of the sequence. The pattern we use to detect these proteins starts two residues before the HTH motif and ends two residues before the end of helix 3. We also developed a profile that covers the entire wHTH, including helix 1 and strand 4, and which allows a more sensitive detection.