{PDOC00366} {PS00356; HTH_LACI_1} {PS50932; HTH_LACI_2} {BEGIN} ********************************************** * LacI-type HTH domain signature and profile * ********************************************** The lacI-type HTH domain is a DNA-binding, helix-turn-helix (HTH) domain of about 50-60 residues present in the lacI/galR family of transcriptional regulators involved in metabolic regulation in prokaryotes. Most of these bacterial regulators recognize sugar-inducers. The family is named after the Escherichia coli lactose operon repressor lacI and galactose operon repressor galR. LacI-type regulators are present in diverse bacterial genera, in the cytoplasm. The 'helix-turn-helix' DNA-binding motif is located in the N-terminal extremity of these transcriptional regulators. The C-terminal part of lacI-type regulators contains several regions that can be involved in (1) binding of inducers, which are sugars and their analogs and (2) oligomerization. The lac repressor is a tetramer, whilst the gal and cyt repressors are dimers. LacI-type transcriptional regulators are important in the coordination of catabolic, metabolic and transport operons [1,2]. Several structures of lacI-type transcriptional regulators have been resolved and their DNA-binding domain encompasses a headpiece, formed by a fold of three helices, followed by a hinge region, which can form a fourth alpha helix or hinge-helix (see ). The helix-turn-helix motif comprises the first and second helices, the second being called the recognition helix. The HTH is involved in DNA-binding into the major groove, while the hinge-helix fits into the minor groove and the complete domain specifically recognizes the operator DNA [3,4]. Some proteins known to contain a lacI-type HTH domain: - Bacillus subtilis ccpA and ccpB, transcriptional regulators involved in the catabolic repression of several operons. - Salmonella typhimurium fruR, the fructose repressor, involved in the regulation of a large number of operons encoding enzymes which take part in central pathways of carbon metabolism. - Escherichia coli lacI, the lactose operon repressor, serving as a model for gene regulation. - Escherichia coli purF and purR, repressors involved in the regulation of enzymes for purine nucleotide synthesis. - Haemophilus influenzae galR, a repressor of the galactose operon. The pattern we developed spans the complete HTH motif, except for the last residue. We also developed a profile that covers the entire HTH and DNA-binding domain, including the hinge-helix and allows a more sensitive detection. -Consensus pattern: [LIVM]-x-[DE]-[LIVM]-A-x(2)-[STAGV]-x-V-[GSTP]-x(2)- [STAG]-[LIVMA]-x(2)-[LIVMFYAN]-[LIVMC] -Sequences known to belong to this class detected by the pattern: ALL, except for rafR. -Other sequence(s) detected in Swiss-Prot: NONE. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: October 2003 / Text revised; profile added. [ 1] Vartak N.B., Reizer J., Reizer A., Gripp J.T., Groisman E.A., Wu L.-F., Tomich J.M., Saier M.H. Jr. "Sequence and evolution of the FruR protein of Salmonella typhimurium: a pleiotropic transcriptional regulatory protein possessing both activator and repressor functions which is homologous to the periplasmic ribose-binding protein." Res. Microbiol. 142:951-963(1991). PubMed=1805309 [ 2] Weickert M.J., Adhya S. "A family of bacterial regulators homologous to Gal and Lac repressors." J. Biol. Chem. 267:15869-15874(1992). PubMed=1639817 [ 3] Nguyen C.C., Saier M.H. Jr. "Phylogenetic, structural and functional analyses of the LacI-GalR family of bacterial transcription factors." FEBS Lett. 377:98-102(1995). PubMed=8543068 [ 4] Mueller-Hill B. Curr. Opin. Microbiol. 1:145-151(1998). -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}