{PDOC50943} {PS50943; HTH_CROC1} {BEGIN} ********************************** * Cro/C1-type HTH domain profile * ********************************** The cro/C1-type HTH domain is a DNA-binding, helix-turn-helix (HTH) domain of about 50-60 residues present in transcriptional regulators. The domain is named after the transcriptional repressors cro and C1 of temperate bacteriophages 434 and lambda, respectively. Besides in bacteriophages, cro/C1-type regulators are present in prokaryotes and in eukaryotes. The helix-turn-helix DNA-binding motif is generally located in the N-terminal part of these transcriptional regulators. The C-terminal part may contain an oligomerization domain, e.g. C1 repressors and CopR act as dimers, while SinR is a tetramer. The cro/C1-type HTH domain also occurs in combination with the TPR repeat and the C-terminal part of C-5 cytosine-specific DNA methylases contains regions related to the enzymatic function (see ). Several structures of cro/C1-type transcriptional repressors have been resolved and their DNA-binding domain encompasses five alpha helices, of which the extremities are less conserved (see ) [1]. The helix-turn-helix motif comprises the second and third helices, the third being called the recognition helix. The HTH is involved in DNA-binding into the major groove, where the recognition helix makes most DNA-contacts. The bacteriophage repressors regulate lysogeny/lytic growth by binding with differential affinity to the operators. These operators show 2-fold symmetry and the repressors bind as dimers. Binding of the repressor to the operator positions the DNA backbone into a slightly bent twist [1,2]. Some proteins known to contain a cro/C1-type HTH domain: - Bacteriophage 434 cro and C1, transcriptional repressors that bind to the operator DNA. Upon induction, proteases in the bacterial host cleave the C1 dimerization domain from the DNA-binding domain, so that genes for the lytic pathway are no longer repressed. - PBSX xre, a repressor protein of the defective prophage in Bacillus. - Bacillus subtilis sinR, a transcriptional repressor for inhibition of sporulation. The structure and function are related to phage repressors [3]. - Bombyx mori (Silk moth) MBF1, multiprotein bridging factor 1, a transcriptional coactivator that mediates transcriptional activation by connecting a general and a gene-specific transcription factor. MBF1 is conserved in eukaryotes from yeast to human [4,5]. - Plasmid pIP501 copR, a transcriptional repressor and activator involved in plasmid copy number regulation. - Escherichia coli nadR, a transcriptional regulator of early NAD biosynthetic genes. - Dictyostelium discoideum (Slime mold) H7, a vegetative specific protein which is deactivated upon the initiation of development. The profile we developed covers the entire DNA-binding domain, from the major part of helix 1, including the helix-turn-helix motif and the major part of helix 5. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: CYNS_AQUAE. -Last update: November 2003 / First entry. [ 1] Aggarwal A.K., Rodgers D.W., Drottar M., Ptashne M., Harrison S.C. "Recognition of a DNA operator by the repressor of phage 434: a view at high resolution." Science 242:899-907(1988). PubMed=3187531 [ 2] Steinmetzer K., Behlke J., Brantl S., Lorenz M. "CopR binds and bends its target DNA: a footprinting and fluorescence resonance energy transfer study." Nucleic Acids Res. 30:2052-2060(2002). PubMed=11972345 [ 3] Lewis R.J., Brannigan J.A., Offen W.A., Smith I., Wilkinson A.J. "An evolutionary link between sporulation and prophage induction in the structure of a repressor:anti-repressor complex." J. Mol. Biol. 283:907-912(1998). PubMed=9799632 [ 4] Takemaru K., Li F.Q., Ueda H., Hirose S. "Multiprotein bridging factor 1 (MBF1) is an evolutionarily conserved transcriptional coactivator that connects a regulatory factor and TATA element-binding protein." Proc. Natl. Acad. Sci. U.S.A. 94:7251-7256(1997). PubMed=9207077 [ 5] Kabe Y., Goto M., Shima D., Imai T., Wada T., Morohashi K., Shirakawa M., Hirose S., Handa H. "The role of human MBF1 as a transcriptional coactivator." J. Biol. Chem. 274:34196-34202(1999). PubMed=10567391 -------------------------------------------------------------------------------- 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}