<p>Prokaryotic cells have a defence mechanism against a sudden heat-shock stress. Commonly, they induce a set of proteins that protect cellular proteins from being denatured by heat. Among such proteins are the GroE and DnaK chaperones whose transcription is regulated by a heat-shock repressor protein HrcA. HrcA is a winged helix-turn-helix repressor that negatively regulates the transcription of dnaK and groE operons by binding the upstream CIRCE (controlling inverted repeat of chaperone expression) element. In <taxon tax_id="1423">Bacillus subtilis</taxon> this element is a perfect 9 base pair inverted repeat separated by a 9 base pair spacer. </p><p> The crystal structure of a heat-inducible transcriptional repressor, HrcA, from <taxon tax_id="2336">Thermotoga maritima</taxon> has been reported at 2.2A resolution. HrcA is composed of three domains: an N-terminal winged helix-turn-helix domain (WHTH), a GAF-like domain, and an inserted dimerizing domain (IDD). The IDD shows a unique structural fold with an anti-parallel beta-sheet composed of three beta-strands sided by four alpha-helices. HrcA crystallises as a dimer, which is formed through hydrophobic contact between the IDDs and a limited contact that involves conserved residues between the GAF-like domains [<cite idref="PUB00037641"/>]. The structural studies suggest that the inactive form of HrcA is the dimer and this is converted to its DNA-binding form by interaction with GroEL, which binds to a conserved C-terminal sequence region [<cite idref="PUB00053432"/>, <cite idref="PUB00037641"/>]. Comparison of the HrcA-CIRCE complexes from B. subtilis and <taxon tax_id="1426">Bacillus thermoglucosidasius</taxon> (Geobacillus thermoglucosidasius), which grow at vastly different ranges of temperature shows that the thermostability profiles were consistent with the difference in the growth temperatures suggesting that HrcA can function as a thermosensor to detect temperature changes in cells [<cite idref="PUB00053433"/>]. Any increase in temperature causes the dissociation of the HrcA from the CIRCE complex with the concomitant activation of transcription of the groE and dnaK operons. </p><p>This domain represents the winged helix-turn-helix DNA-binding domain which is located close to the N terminus of HrcA. This domain is also found at the N terminus of a set of uncharacterised proteins that have two C-terminal CBS domains. </p> Winged helix-turn-helix transcription repressor, HrcA DNA-binding domain