Secondary literature sources for HTH_LACI
The following references were automatically generated.
- Swint-Kruse L, Elam CR, Lin JW, Wycuff DR, Shive Matthews K
- Plasticity of quaternary structure: twenty-two ways to form a LacI dimer.
- Protein Sci. 2001; 10: 262-76
- Display abstract
The repressor proteins of the LacI/GalR family exhibit significant similarity in their secondary and tertiary structures despite less than 35% identity in their primary sequences. Furthermore, the core domains of these oligomeric repressors, which mediate dimerization, are homologous with the monomeric periplasmic binding proteins, extending the issue of plasticity to quaternary structure. To elucidate the determinants of assembly, a structure-based alignment has been created for three repressors and four periplasmic binding proteins. Contact maps have also been constructed for the three repressor interfaces to distinguish any conserved interactions. These analyses show few strict requirements for assembly of the core N-subdomain interface. The interfaces of repressor core C-subdomains are well conserved at the structural level, and their primary sequences differ significantly from the monomeric periplasmic binding proteins at positions equivalent to LacI 281 and 282. However, previous biochemical and phenotypic analyses indicate that LacI tolerates many mutations at 281. Mutations at LacI 282 were shown to abrogate assembly, but for Y282D this could be compensated by a second-site mutation in the core N-subdomain at K84 to L or A. Using the link between LacI assembly and function, we have further identified 22 second-site mutations that compensate the Y282D dimerization defect in vivo. The sites of these mutations fall into several structural regions, each of which may influence assembly by a different mechanism. Thus, the 360-amino acid scaffold of LacI allows plasticity of its quaternary structure. The periplasmic binding proteins may require only minimal changes to facilitate oligomerization similar to the repressor proteins.
- Bouhouche N, Syvanen M, Kado CI
- The origin of prokaryotic C2H2 zinc finger regulators.
- Trends Microbiol. 2000; 8: 77-81
- Display abstract
C2H2 zinc finger bearing proteins are a large superfamily of nucleic acid binding proteins, which constitute a major subset of eukaryotic transcription factors. Although originally thought to occur only in eukaryotes, a novel C2H2 zinc finger transcription factor, Ros, which regulates both prokaryotic and eukaryotic promoters has been found in bacteria. Phylogenically, Ros is distantly related to eukaryotic zinc finger regulators.
- Alekshun MN, Kim YS, Levy SB
- Mutational analysis of MarR, the negative regulator of marRAB expression in Escherichia coli, suggests the presence of two regions required for DNA binding.
- Mol Microbiol. 2000; 35: 1394-404
- Display abstract
MarR, the negative regulator of the Escherichia coli multiple antibiotic resistance (marRAB) operon, is a member of a newly recognized family of regulatory proteins. The amino acid sequences of these proteins do not display any apparent homologies to the DNA binding domains of prokaryotic transcription regulators and a DNA binding motif for any one of the MarR homologues is currently unknown. In order to define regions of MarR required for DNA binding, mutant repressors, selected based on their ability to interfere with (negatively complement) the activity of wild-type MarR, were isolated. As determined using gel mobility shift assays, 13 out of 14 negative complementing mutants tested were unable to bind DNA in vitro. Three negative complementing alleles presumably specify truncated repressors and one of these proteins, a 120 residue MarR, can bind DNA in vitro. Most of the negative complementing mutations were clustered within two areas of MarR with features related to a helix-turn-helix DNA binding motif. These regions are presumed to be required for the DNA binding activity of the repressor.
- Matthews KS, Nichols JC
- Lactose repressor protein: functional properties and structure.
- Prog Nucleic Acid Res Mol Biol. 1998; 58: 127-64
- Display abstract
The lactose repressor protein (LacI), the prototype for genetic regulatory proteins, controls expression of lactose metabolic genes by binding to its cognate operator sequences in E. coli DNA. Inducer binding elicits a conformational change that diminishes affinity for operator sequences with no effect on nonspecific binding. The release of operator is followed by synthesis of mRNA encoding the enzymes for lactose utilization. Genetic, chemical and physical studies provided detailed insight into the function of this protein prior to the recent completion of X-ray crystallographic structures. The structural information can now be correlated with the phenotypic data for numerous mutants. These structures also provide the opportunity for physical and chemical studies on mutants designed to examine various aspects of lac repressor structure and function. In addition to providing insight into protein structure-function correlations, LacI has been utilized in a wide variety of applications both in prokaryotic gene expression and in eukaryotic gene regulation and studies of mutagenesis.
- Muller-Hill B
- Some repressors of bacterial transcription.
- Curr Opin Microbiol. 1998; 1: 145-51
- Display abstract
For a long time, repression of transcription in Escherichia coli was thought to be generally caused by one repressor binding to one operator. Recent work has indicated the frequent presence of auxiliary operators and helper proteins. The recent solution of the X-ray structures of Lac and Pur repressors were breakthroughs; yet, it has become painfully clear that important aspects of repression are still not understood.
- Saha S, Brickman JM, Lehming N, Ptashne M
- New eukaryotic transcriptional repressors.
- Nature. 1993; 363: 648-52
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Transcriptional activating sequences have been described that are encoded by parts of the genome of Escherichia coli. These acidic peptides, fused to a DNA-binding fragment of the yeast transcriptional activator GAL4, activate transcription of a gene in a wide array of eukaryotes, provided that gene bears GAL4-binding sites nearby. Here we describe an E. coli-encoded sequence that, when attached to the same DNA-binding fragment (GAL4(1-147)), converts that fragment into a repressor. Thus, as assayed in yeast or in vitro in yeast extracts, this molecule represses transcription when bound upstream of a variety of different activators. Two additional repressing regions that work when tethered upstream, a multiple mutant derivative of the original isolate and a synthetic peptide are, like the original isolate, highly basic. At least one activator can be inhibited by the mutant but not by the parental repressing region. These and other findings suggest that these repressing regions interact with and inhibit the activity of activating regions bound nearby on DNA.
- Somerville R
- The Trp repressor, a ligand-activated regulatory protein.
- Prog Nucleic Acid Res Mol Biol. 1992; 42: 1-38
- Schnarr M, Oertel-Buchheit P, Kazmaier M, Granger-Schnarr M
- DNA binding properties of the LexA repressor.
- Biochimie. 1991; 73: 423-31
- Display abstract
The LexA repressor from Escherichia coli negatively regulates the transcription of about 20 different genes upon binding with variable affinity to single-, double- or even triple-operators as in the case of the recN gene. Binding of LexA to multiple operators is cooperative if the spacing between these operators is favorable. LexA recognizes DNA via its amino-terminal domain. The three-dimensional structure of this domain has been determined by NMR measurements. It contains three alpha-helices spanning residues 8-20, 28-35 and 41-54. In view of this structure, but also according to homology considerations and the unusual contact pattern with the DNA backbone, the LexA repressor is not a normal helix-turn-helix DNA binding protein like for example phage lambda repressor. LexA is at best a distant relative of this class of transcription factors and should probably be considered as a protein that contains a new DNA binding motif. A cluster of LexA mutant repressors deficient in DNA binding falling into the third helix (residues 41-54 bp) suggests that this helix is involved in DNA recognition.
