Abstract
We show here, both in vivo and in vitro, that P22 repressor binds co-operatively to operator sites separated by an integral number of turns of the DNA helix. We measure this co-operativity in vivo using an assay in which repression of a promoter requires co-operative binding of P22 repressors to two separated (non-adjacent) operator sites. We report the isolation of mutant repressors that have high affinity for single operator sites, but are defective in co-operative binding. Six different mutants, all bearing single amino acid changes in the carboxyl domain, have been isolated. We purified the two mutants most deficient in co-operative binding, and found that they bind non-co-operatively in vitro to adjacent as well as to non-adjacent pairs of operator sites.
MeSH Terms
Bacteriophage lambda/genetics
Base Sequence
DNA, Viral/genetics,metabolism
Escherichia coli/genetics
Molecular Sequence Data
Mutation
Plasmids
Promoter Regions, Genetic
Protein Binding
Repressor Proteins/genetics,isolation & purification,metabolism
Salmonella/genetics
Salmonella Phages/genetics
Transcription Factors/genetics
beta-Galactosidase/genetics
Chemicals
DNA, Viral
Repressor Proteins
Transcription Factors
beta-Galactosidase
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Valenzuela D
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.
Ptashne M
References (30)
30 references, click to expand
-
Genetic studies of the lac repressor. III. Additional correlation of mutational sites with specific amino acid residues.
J Mol Biol. 1977 Dec 15;117(3):525-67
PMID: 609095
-
The lambda and P22 phage repressors.
J Biomol Struct Dyn. 1983 Dec;1(4):1011-22
PMID: 6242868
-
Construction of plasmids that produce phage P22 repressor.
Gene. 1981 Mar;13(2):153-61
PMID: 6453742
-
Primary structure of the phage P22 repressor and its gene c2.
Biochemistry. 1981 Jun 9;20(12):3591-8
PMID: 7260059
-
lambda Repressor and cro--components of an efficient molecular switch.
Nature. 1981 Nov 19;294(5838):217-23
PMID: 6457992
-
Control of transcription by the bacteriophage P22 repressor.
J Mol Biol. 1982 May 5;157(1):21-48
PMID: 6809952
-
P22 c2 repressor. Domain structure and function.
J Biol Chem. 1983 Sep 10;258(17):10536-42
PMID: 6554278
-
Deletion analysis of the CAP-cAMP binding site of the Escherichia coli lactose promoter.
Nucleic Acids Res. 1984 Jul 11;12(13):5449-64
PMID: 6087287
-
An operator at -280 base pairs that is required for repression of araBAD operon promoter: addition of DNA helical turns between the operator and promoter cyclically hinders repression.
Proc Natl Acad Sci U S A. 1984 Aug;81(16):5017-20
PMID: 6089170
-
Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors.
Gene. 1985;33(1):103-19
PMID: 2985470
-
Supercoil sequencing: a fast and simple method for sequencing plasmid DNA.
DNA. 1985 Apr;4(2):165-70
PMID: 3996185
-
Changing the binding specificity of a repressor by redesigning an alpha-helix.
Nature. 1985 Aug 15-21;316(6029):601-5
PMID: 4033758
-
Cooperative binding of lambda repressors to sites separated by integral turns of the DNA helix.
Cell. 1986 Mar 14;44(5):681-7
PMID: 3948245
-
The DNA loop model for ara repression: AraC protein occupies the proposed loop sites in vivo and repression-negative mutations lie in these same sites.
Proc Natl Acad Sci U S A. 1986 Jun;83(11):3654-8
PMID: 3520549
-
Gene regulation by proteins acting nearby and at a distance.
Nature. 1986 Aug 21-27;322(6081):697-701
PMID: 3018583
-
DNA loops induced by cooperative binding of lambda repressor.
Nature. 1986 Aug 21-27;322(6081):750-2
PMID: 3748156
-
A new-specificity mutant of 434 repressor that defines an amino acid-base pair contact.
Nature. 1987 Apr 30-May 6;326(6116):888-91
PMID: 3553961
-
Gene regulation: why should DNA loop?
Nature. 1987 Jun 4-10;327(6121):369-70
PMID: 3587357
-
lac repressor forms loops with linear DNA carrying two suitably spaced lac operators.
EMBO J. 1987 May;6(5):1481-91
PMID: 3301328
-
Specific destruction of the second lac operator decreases repression of the lac operon in Escherichia coli fivefold.
J Mol Biol. 1987 Jun 20;195(4):949-52
PMID: 3116268
-
Lac repressor is a transient gene-activating protein.
Cell. 1987 Dec 4;51(5):699-707
PMID: 3315229
-
A repressor heterodimer binds to a chimeric operator.
Proc Natl Acad Sci U S A. 1988 Aug;85(16):5834-8
PMID: 3413061
-
How eukaryotic transcriptional activators work.
Nature. 1988 Oct 20;335(6192):683-9
PMID: 3050531
-
Interaction at a distance between lambda repressors disrupts gene activation.
Nature. 1988 Nov 24;336(6197):353-7
PMID: 2973565
-
Dual mechanism of repression at a distance in the lac operon.
Proc Natl Acad Sci U S A. 1988 Dec;85(23):8968-72
PMID: 3143112
-
Promoters largely determine the efficiency of repressor action.
Proc Natl Acad Sci U S A. 1988 Dec;85(23):8973-7
PMID: 3057497
-
Interaction of spatially separated protein-DNA complexes for control of gene expression: operator conversions.
Proc Natl Acad Sci U S A. 1988 Dec;85(24):9683-7
PMID: 3059350
-
The gamma delta resolvase bends the res site into a recombinogenic complex.
EMBO J. 1988 Nov;7(11):3609-16
PMID: 2850169
-
Single-stranded DNA 'blue' T7 promoter plasmids: a versatile tandem promoter system for cloning and protein engineering.
Protein Eng. 1986 Oct-Nov;1(1):67-74
PMID: 3507689
-
E. coli RNA polymerase interacts homologously with two different promoters.
Cell. 1980 Jun;20(2):269-81
PMID: 6248238