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EMBO J. Aug 1992; 11(8): 3031–3038.
PMCID: PMC556785

Lac repressor with the helix-turn-helix motif of lambda cro binds to lac operator.


Lac repressor, lambda cro protein and their operator complexes are structurally, biochemically and genetically well analysed. Both proteins contain a helix-turn-helix (HTH) motif which they use to bind specifically to their operators. The DNA sequences 5'-GTGA-3' and 5'-TCAC-3' recognized in palindromic lac operator are the same as in lambda operator but their order is inverted form head to head to tail to tail. Different modes of aggregation of the monomers of the two proteins determine the different arrangements of the HTH motifs. Here we show that the HTH motif of lambda cro protein can replace the HTH motif of Lac repressor without changing its specificity. Such hybrid Lac repressor is unstable. It binds in vitro more weakly than Lac repressor but with the same specificity to ideal lac operator. It does not bind to consensus lambda operator.

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  • Adler K, Beyreuther K, Fanning E, Geisler N, Gronenborn B, Klemm A, Müller-Hill B, Pfahl M, Schmitz A. How lac repressor binds to DNA. Nature. 1972 Jun 9;237(5354):322–327. [PubMed]
  • Alberti S, Oehler S, von Wilcken-Bergmann B, Krämer H, Müller-Hill B. Dimer-to-tetramer assembly of Lac repressor involves a leucine heptad repeat. New Biol. 1991 Jan;3(1):57–62. [PubMed]
  • Anderson WF, Ohlendorf DH, Takeda Y, Matthews BW. Structure of the cro repressor from bacteriophage lambda and its interaction with DNA. Nature. 1981 Apr 30;290(5809):754–758. [PubMed]
  • Benson N, Youderian P. Phage lambda Cro protein and cI repressor use two different patterns of specific protein-DNA interactions to achieve sequence specificity in vivo. Genetics. 1989 Jan;121(1):5–12. [PMC free article] [PubMed]
  • Boelens R, Scheek RM, van Boom JH, Kaptein R. Complex of lac repressor headpiece with a 14 base-pair lac operator fragment studied by two-dimensional nuclear magnetic resonance. J Mol Biol. 1987 Jan 5;193(1):213–216. [PubMed]
  • Blackwell TK, Kretzner L, Blackwood EM, Eisenman RN, Weintraub H. Sequence-specific DNA binding by the c-Myc protein. Science. 1990 Nov 23;250(4984):1149–1151. [PubMed]
  • Brennan RG, Roderick SL, Takeda Y, Matthews BW. Protein-DNA conformational changes in the crystal structure of a lambda Cro-operator complex. Proc Natl Acad Sci U S A. 1990 Oct;87(20):8165–8169. [PMC free article] [PubMed]
  • Dang CV, Dolde C, Gillison ML, Kato GJ. Discrimination between related DNA sites by a single amino acid residue of Myc-related basic-helix-loop-helix proteins. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):599–602. [PMC free article] [PubMed]
  • Galas DJ, Schmitz A. DNAse footprinting: a simple method for the detection of protein-DNA binding specificity. Nucleic Acids Res. 1978 Sep;5(9):3157–3170. [PMC free article] [PubMed]
  • Geisler N, Weber K. Isolation of amino-terminal fragment of lactose repressor necessary for DNA binding. Biochemistry. 1977 Mar 8;16(5):938–943. [PubMed]
  • Hochschild A, Ptashne M. Homologous interactions of lambda repressor and lambda Cro with the lambda operator. Cell. 1986 Mar 28;44(6):925–933. [PubMed]
  • Hochschild A, Douhan J, 3rd, Ptashne M. How lambda repressor and lambda Cro distinguish between OR1 and OR3. Cell. 1986 Dec 5;47(5):807–816. [PubMed]
  • JACOB F, MONOD J. Genetic regulatory mechanisms in the synthesis of proteins. J Mol Biol. 1961 Jun;3:318–356. [PubMed]
  • Jobe A, Bourgeois S. The lac repressor-operator interaction. VII. A repressor with unique binding properties: the X86 repressor. J Mol Biol. 1972 Dec 14;72(1):139–152. [PubMed]
  • Jordan SR, Pabo CO. Structure of the lambda complex at 2.5 A resolution: details of the repressor-operator interactions. Science. 1988 Nov 11;242(4880):893–899. [PubMed]
  • Kaptein R, Zuiderweg ER, Scheek RM, Boelens R, van Gunsteren WF. A protein structure from nuclear magnetic resonance data. lac repressor headpiece. J Mol Biol. 1985 Mar 5;182(1):179–182. [PubMed]
  • Kisters-Woike B, Lehming N, Sartorius J, von Wilcken-Bergmann B, Müller-Hill B. A model of the lac repressor-operator complex based on physical and genetic data. Eur J Biochem. 1991 Jun 1;198(2):411–419. [PubMed]
  • Lamerichs RM, Boelens R, van der Marel GA, van Boom JH, Kaptein R, Buck F, Fera B, Rüterjans H. H NMR study of a complex between the lac repressor headpiece and a 22 base pair symmetric lac operator. Biochemistry. 1989 Apr 4;28(7):2985–2991. [PubMed]
  • Lehming N, Sartorius J, Niemöller M, Genenger G, v Wilcken-Bergmann B, Müller-Hill B. The interaction of the recognition helix of lac repressor with lac operator. EMBO J. 1987 Oct;6(10):3145–3153. [PMC free article] [PubMed]
  • Lehming N, Sartorius J, Oehler S, von Wilcken-Bergmann B, Müller-Hill B. Recognition helices of lac and lambda repressor are oriented in opposite directions and recognize similar DNA sequences. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7947–7951. [PMC free article] [PubMed]
  • Lehming N, Sartorius J, Kisters-Woike B, von Wilcken-Bergmann B, Müller-Hill B. Mutant lac repressors with new specificities hint at rules for protein--DNA recognition. EMBO J. 1990 Mar;9(3):615–621. [PMC free article] [PubMed]
  • Matthews BW, Ohlendorf DH, Anderson WF, Takeda Y. Structure of the DNA-binding region of lac repressor inferred from its homology with cro repressor. Proc Natl Acad Sci U S A. 1982 Mar;79(5):1428–1432. [PMC free article] [PubMed]
  • Maxam AM, Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. [PMC free article] [PubMed]
  • Ogata RT, Gilbert W. An amino-terminal fragment of lac repressor binds specifically to lac operator. Proc Natl Acad Sci U S A. 1978 Dec;75(12):5851–5854. [PMC free article] [PubMed]
  • Ohlendorf DH, Anderson WF, Fisher RG, Takeda Y, Matthews BW. The molecular basis of DNA-protein recognition inferred from the structure of cro repressor. Nature. 1982 Aug 19;298(5876):718–723. [PubMed]
  • O'Neil KT, Hoess RH, DeGrado WF. Design of DNA-binding peptides based on the leucine zipper motif. Science. 1990 Aug 17;249(4970):774–778. [PubMed]
  • Pakula AA, Young VB, Sauer RT. Bacteriophage lambda cro mutations: effects on activity and intracellular degradation. Proc Natl Acad Sci U S A. 1986 Dec;83(23):8829–8833. [PMC free article] [PubMed]
  • Pfahl M. lac Repressor-operator interaction. Analysis of the X86 repressor mutant. J Mol Biol. 1976 Sep 25;106(3):857–869. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Sartorius J, Lehming N, Kisters-Woike B, von Wilcken-Bergmann B, Müller-Hill B. The roles of residues 5 and 9 of the recognition helix of Lac repressor in lac operator binding. J Mol Biol. 1991 Mar 20;218(2):313–321. [PubMed]
  • Schlotmann M, Beyreuther K. Degradation of the DNA-binding domain of wild-type and i-d lac repressors in Escherichia coli. Eur J Biochem. 1979 Mar 15;95(1):39–49. [PubMed]
  • Schmitz A, Coulondre C, Miller JH. Genetic studies of the lac repressor. V. Repressors which bind operator more tightly generated by suppression and reversion of nonsense mutations. J Mol Biol. 1978 Aug 15;123(3):431–454. [PubMed]
  • Simons A, Tils D, von Wilcken-Bergmann B, Müller-Hill B. Possible ideal lac operator: Escherichia coli lac operator-like sequences from eukaryotic genomes lack the central G X C pair. Proc Natl Acad Sci U S A. 1984 Mar;81(6):1624–1628. [PMC free article] [PubMed]
  • Takeda Y, Kim JG, Caday CG, Steers E, Jr, Ohlendorf DH, Anderson WF, Matthews BW. Different interactions used by Cro repressor in specific and nonspecific DNA binding. J Biol Chem. 1986 Jul 5;261(19):8608–8616. [PubMed]
  • Takeda Y, Sarai A, Rivera VM. Analysis of the sequence-specific interactions between Cro repressor and operator DNA by systematic base substitution experiments. Proc Natl Acad Sci U S A. 1989 Jan;86(2):439–443. [PMC free article] [PubMed]
  • Vinson CR, Sigler PB, McKnight SL. Scissors-grip model for DNA recognition by a family of leucine zipper proteins. Science. 1989 Nov 17;246(4932):911–916. [PubMed]
  • Wharton RP, Brown EL, Ptashne M. Substituting an alpha-helix switches the sequence-specific DNA interactions of a repressor. Cell. 1984 Sep;38(2):361–369. [PubMed]
  • Yamamoto KK, Gonzalez GA, Biggs WH, 3rd, Montminy MR. Phosphorylation-induced binding and transcriptional efficacy of nuclear factor CREB. Nature. 1988 Aug 11;334(6182):494–498. [PubMed]

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