|PROSITE documentation PDOC00830|
The tetR-type HTH domain is a DNA-binding, helix-turn-helix (HTH) domain of about 60 residues present in the tetR family of prokaryotic transcription regulators. Several of these bacterial regulators are repressors of genes and operons for membrane transport and cell envelope permeability. The family is named after the tetracycline repressor tetR of enterobacteria found on Tn10 and other transposons and plasmids. The 'helix-turn-helix' DNA-binding motif is located in the N-terminal extremity of these transcriptional regulators . The C-terminal part of tetR-type regulators contains several regions that can be involved in (1) binding of inducers, which can be drugs, and (2) oligomerization. The tetR and camR proteins are dimers, whilst qacR binds its operator as a pair of dimers and ethR seems to bind as an octamer [2,3,4]. TetR-type transcription regulators include several bacterial regulators of drug export systems that protect pathogenic bacteria against antibiotics, antiseptics, disinfectants and host-encoded antimicrobials .
Several crystal structures of tetR-type transcription regulators have been resolved and their DNA-binding domains are formed by a three-helix bundle (H1-H3) and the N-terminal part of the following helix 4, which contributes to the hydrophobic center of the DNA-binding domain and links it to the regulatory domain . The helix-turn-helix motif comprises the second and third helices, the third being called the recognition helix as it binds into the DNA major groove (see <PDB:1JT0>). The recognition helix of the tetR-type HTH is shorter than in most HTHs.
Some proteins known to contain a tetR-type HTH domain:
As a signature pattern we selected a conserved region that starts six residues before the helix-turn-helix motif and ends seven residues after the H-T-H motif. We also developed a profile that covers the entire HTH and DNA-binding domain, from the first helix and including the major part of the fourth helix, and allows a more sensitive detection.Expert(s) to contact by email:
December 2004 / Pattern and text revised.
PROSITE methods (with tools and information) covered by this documentation:
|1||Authors||Aramaki H. Yagi N. Suzuki M.|
|Title||Residues important for the function of a multihelical DNA binding domain in the new transcription factor family of Cam and Tet repressors.|
|Source||Protein Eng. 8:1259-1266(1995).|
|2||Authors||Orth P. Schnappinger D. Hillen W. Saenger W. Hinrichs W.|
|Title||Structural basis of gene regulation by the tetracycline inducible Tet repressor-operator system.|
|Source||Nat. Struct. Biol. 7:215-219(2000).|
|3||Authors||Grkovic S. Brown M.H. Skurray R.A.|
|Title||Regulation of bacterial drug export systems.|
|Source||Microbiol. Mol. Biol. Rev. 66:671-701(2002).|
|4||Authors||Engohang-Ndong J. Baillat D. Aumercier M. Bellefontaine F. Besra G.S. Locht C. Baulard A.R.|
|Source||Mol. Microbiol. 51:175-188(2004).|
|5||Authors||Schumacher M.A. Miller M.C. Grkovic S. Brown M.H. Skurray R.A. Brennan R.G.|
|Title||Structural mechanisms of QacR induction and multidrug recognition.|