PROSITE documentation PDOC01035

Rrf2-type HTH domain profile

The rrf2-type HTH domain is a DNA-binding, winged helix-turn-helix (wHTH) domain of about 130 residues present in transcription regulators of the rrf2 family. This family of bacterial regulators is named after Desulfovibrio vulgaris rrf2, a regulator of the hmc operon which encodes iron-sulfur-containing proteins as well as other proteins involved in electron transport [1,2]. Other rrf2-type HTH proteins are regulators of genes involved in nitrite or iron metabolism, or nitric oxide detoxification.

The N-terminal part of the domain shows similarity to the iclR-type (see <PDOC00807>), the gntR-type (see <PDOC00042>) and marR-type HTH (see <PDOC00861>), wherein the DNA-binding HTH motif is followed by a β-hairpin which is called the wing. The C-terminal part of the rrf2-type HTH domain in most cases contains 3 conserved cysteine residues that may bind an [2Fe-2S] cluster, like in iscR and nsrR [3,4,5,6,7,8]. The nsrR regulator, which contains an nitrogen-oxides-sensing Fe-S cluster that is required for DNA binding, is implicated in denitrification and/or NO detoxification in diverse pathogenic and environmental bacteria.

Some proteins known to contain a rrf2-type HTH domain:

• Desulfovibrio vulgaris protein rrf2, a repressor of the hmc operon encoding a cytochrome redox complex for electron transport from hydrogen to sulfate.
• Escherichia coli iscR (for iron-sulfur cluster regulator), a transcription repressor of the isc operon encoding Fe-S assembly proteins. IscR reversibly binds a [2Fe-2S] cluster and functions as an autoregulator. Demetallated iscR (apo-iscR) acts as an activator under oxidative and Fe-limited conditions.
• Nitrosomonas europaea nsrR, a nitrite sensitive transcription repressor of nitrite reductase, involved in detoxification of nitrite.
• Escherichia coli nsrR, a nitric oxide sensitive transcription regulator of genes that may protect the cell against NO-stress (NO is a damaging agent of Fe-S clusters).
• Bacillus subtilis protein nsrR, a NO-responsive transcription regulator.
• Streptomyces coelicolor nsrR, a transcription regulator containing an NO-sensitive [2Fe-2S] cluster that is required for DNA-binding.
• Rhizobium leguminosarum rirA (rhizobial iron regulator), an iron-responsive regulator involved in Fe uptake.
• Bacillus subtilis protein yrzC.
• Mycobacterium tuberculosis protein Rv1287/MT1325.
• Synechocystis strain PCC 6803 protein slr0846.

The pattern we use to detect these proteins is located in the central part of these proteins and covers the stronger conserved region [2], 'the wing', which starts directly C-terminal to the 'helix-turn-helix' motif of these proteins. We also developed a profile that covers the entire rrf2-type wHTH, including the C-terminal region which may bind an iron-sulfur cluster.