PROSITE documentation PDOC50943
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 <PDOC00089>).

Several structures of cro/C1-type transcriptional repressors have been resolved and their DNA-binding domain encompasses five α helices, of which the extremities are less conserved (see <PDB:2OR1>) [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.

Last update:

November 2003 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

HTH_CROC1, PS50943; Cro/C1-type HTH domain profile  (MATRIX)


1AuthorsAggarwal A.K. Rodgers D.W. Drottar M. Ptashne M. Harrison S.C.
TitleRecognition of a DNA operator by the repressor of phage 434: a view at high resolution.
SourceScience 242:899-907(1988).
PubMed ID3187531

2AuthorsSteinmetzer K. Behlke J. Brantl S. Lorenz M.
TitleCopR binds and bends its target DNA: a footprinting and fluorescence resonance energy transfer study.
SourceNucleic Acids Res. 30:2052-2060(2002).
PubMed ID11972345

3AuthorsLewis R.J. Brannigan J.A. Offen W.A. Smith I. Wilkinson A.J.
TitleAn evolutionary link between sporulation and prophage induction in the structure of a repressor:anti-repressor complex.
SourceJ. Mol. Biol. 283:907-912(1998).
PubMed ID9799632

4AuthorsTakemaru K. Li F.Q. Ueda H. Hirose S.
TitleMultiprotein bridging factor 1 (MBF1) is an evolutionarily conserved transcriptional coactivator that connects a regulatory factor and TATA element-binding protein.
SourceProc. Natl. Acad. Sci. U.S.A. 94:7251-7256(1997).
PubMed ID9207077

5AuthorsKabe Y. Goto M. Shima D. Imai T. Wada T. Morohashi K. Shirakawa M. Hirose S. Handa H.
TitleThe role of human MBF1 as a transcriptional coactivator.
SourceJ. Biol. Chem. 274:34196-34202(1999).
PubMed ID10567391

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