Repressor
Encyclopedia
In molecular genetics
, a repressor is a DNA-binding protein
that regulates the expression
of one or more genes by binding to the operator
and blocking the attachment of RNA polymerase to the promoter, thus preventing transcription
of the genes. This blocking of expression is called repression.
Repressor proteins are coded for by regulator gene
s. Repressor proteins then attach to a DNA
segment known as the operator. By binding to the operator, the repressor protein prevents the RNA polymerase
from creating messenger RNA
.
If an inducer, a molecule that initiates the gene expression, is present, then it can interact with the repressor protein and detach it from the operator. RNA polymerase then can transcribe the message (expressing the gene). A corepressor is a molecule that can bind to repressor and make it bind to the operator tightly, which decreases transcription. A repressor that binds with a corepressor is termed an aporepressor or inactive repressor. One type of aporepressor is the trp repressor, an important metabolic protein in bacteria.
The above mechanism of repression is a type of a feedback mechanism because it only allows transcription to occur if a certain condition is present: the presence of specific inducer(s).
repressor MetJ.MetJ interacts with DNA
bases via a pair of α-helices. MetJ is a homodimer consisting of two monomers, which each provides a beta ribbon and an alpha helix
. Together, the beta ribbons of each monomer come together to form an antiparallel
beta-sheet which binds to the DNA operator
("Met box") in its major groove. Once bound, the MetJ dimer
interacts with another MetJ dimer bound to the complementary strand of the operator via its alpha helices. AdoMet binds to a pocket in MetJ that DOES NOT overlap the site of DNA binding.
The Met box has the sequence AGACGTCT which is a palindrome
(it shows dyad symmetry
) allowing the same sequence to be recognised on either strand of the DNA. The junction between C and G in the middle of the Met box contains a pyrimidine-purine step that becomes positively supercoiled
forming a kink in the phosphodiester backbone. This is how the protein checks for the recognition site as it allows the DNA duplex to follow the shape of the protein. In other words, recognition happens through indirect readout of the structural parameters of the DNA, rather than via specific base sequence recognition.
Each MetJ dimer contains two binding sites for the cofactor
S-Adenosyl methionine
(SAM) which is a product in the biosynthesis of methionine. When SAM is present it binds to the MetJ protein increasing its affinity for its cognate operator site which halts transcription of genes involved in methionine synthesis. When SAM concentration becomes low the repressor dissociates from the operator site allowing more methionine to be produced.
Another example is the lac operon
of the bacteria Escherichia coli
. the Lac repressor is constitutively expressed and always bound to the operator region of the promoter, interfering with the ability of RNAP to bind to the promoter and transcribe the lac operon. In the presence of lactose
, the repressor changes conformation and falls off the operator and RNAP is able to bind to the promoter. Lactose is called an inducer because it inactivates the repressor and induces transcription.
Molecular genetics
Molecular genetics is the field of biology and genetics that studies the structure and function of genes at a molecular level. The field studies how the genes are transferred from generation to generation. Molecular genetics employs the methods of genetics and molecular biology...
, a repressor is a DNA-binding protein
DNA-binding protein
DNA-binding proteins are proteins that are composed of DNA-binding domains and thus have a specific or general affinity for either single or double stranded DNA. Sequence-specific DNA-binding proteins generally interact with the major groove of B-DNA, because it exposes more functional groups that...
that regulates the expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
of one or more genes by binding to the operator
Operator (biology)
In genetics, an operator is a segment of DNA to which a transcription factor protein binds. It is classically defined in the lac operon as a segment between the promoter and the genes of the operon. In the case of a repressor, the repressor protein physically obstructs the RNA polymerase from...
and blocking the attachment of RNA polymerase to the promoter, thus preventing transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
of the genes. This blocking of expression is called repression.
Repressor proteins are coded for by regulator gene
Regulator gene
A regulator gene, regulator, or regulatory gene is a gene involved in controlling the expression of one or more other genes. A regulator gene may encode a protein, or it may work at the level of RNA, as in the case of genes encoding microRNAs....
s. Repressor proteins then attach to a DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
segment known as the operator. By binding to the operator, the repressor protein prevents the RNA polymerase
RNA polymerase
RNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...
from creating messenger RNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
.
If an inducer, a molecule that initiates the gene expression, is present, then it can interact with the repressor protein and detach it from the operator. RNA polymerase then can transcribe the message (expressing the gene). A corepressor is a molecule that can bind to repressor and make it bind to the operator tightly, which decreases transcription. A repressor that binds with a corepressor is termed an aporepressor or inactive repressor. One type of aporepressor is the trp repressor, an important metabolic protein in bacteria.
The above mechanism of repression is a type of a feedback mechanism because it only allows transcription to occur if a certain condition is present: the presence of specific inducer(s).
Examples
An example of a repressor protein is the methionineMethionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
repressor MetJ.MetJ interacts with DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
bases via a pair of α-helices. MetJ is a homodimer consisting of two monomers, which each provides a beta ribbon and an alpha helix
Alpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
. Together, the beta ribbons of each monomer come together to form an antiparallel
Antiparallel (biochemistry)
In biochemistry, two molecules are antiparallel if they run side-by-side in opposite directions or when both strands are complimentary to each other....
beta-sheet which binds to the DNA operator
Operator (biology)
In genetics, an operator is a segment of DNA to which a transcription factor protein binds. It is classically defined in the lac operon as a segment between the promoter and the genes of the operon. In the case of a repressor, the repressor protein physically obstructs the RNA polymerase from...
("Met box") in its major groove. Once bound, the MetJ dimer
Protein dimer
In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules like proteins or nucleic acids...
interacts with another MetJ dimer bound to the complementary strand of the operator via its alpha helices. AdoMet binds to a pocket in MetJ that DOES NOT overlap the site of DNA binding.
The Met box has the sequence AGACGTCT which is a palindrome
Palindrome
A palindrome is a word, phrase, number, or other sequence of units that can be read the same way in either direction, with general allowances for adjustments to punctuation and word dividers....
(it shows dyad symmetry
Dyad symmetry
In genetics, dyad symmetry refers to two areas of a DNA strand whose base pair sequences are inverted repeats of each other. They are often described as palindromes....
) allowing the same sequence to be recognised on either strand of the DNA. The junction between C and G in the middle of the Met box contains a pyrimidine-purine step that becomes positively supercoiled
DNA supercoil
DNA supercoiling refers to the over- or under-winding of a DNA strand, and is an expression of the strain on the polymer. Supercoiling is important in a number of biological processes, such as compacting DNA. Additionally, certain enzymes such as topoisomerases are able to change DNA topology to...
forming a kink in the phosphodiester backbone. This is how the protein checks for the recognition site as it allows the DNA duplex to follow the shape of the protein. In other words, recognition happens through indirect readout of the structural parameters of the DNA, rather than via specific base sequence recognition.
Each MetJ dimer contains two binding sites for the cofactor
Cofactor (biochemistry)
A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....
S-Adenosyl methionine
S-Adenosyl methionine
S-Adenosyl methionine is a common cosubstrate involved in methyl group transfers. SAM was first discovered in Italy by G. L. Cantoni in 1952. It is made from adenosine triphosphate and methionine by methionine adenosyltransferase . Transmethylation, transsulfuration, and aminopropylation are the...
(SAM) which is a product in the biosynthesis of methionine. When SAM is present it binds to the MetJ protein increasing its affinity for its cognate operator site which halts transcription of genes involved in methionine synthesis. When SAM concentration becomes low the repressor dissociates from the operator site allowing more methionine to be produced.
Another example is the lac operon
Lac operon
The lac operon is an operon required for the transport and metabolism of lactose in Escherichia coli and some other enteric bacteria. It consists of three adjacent structural genes, lacZ, lacY and lacA. The lac operon is regulated by several factors including the availability of glucose and of...
of the bacteria Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
. the Lac repressor is constitutively expressed and always bound to the operator region of the promoter, interfering with the ability of RNAP to bind to the promoter and transcribe the lac operon. In the presence of lactose
Lactose
Lactose is a disaccharide sugar that is found most notably in milk and is formed from galactose and glucose. Lactose makes up around 2~8% of milk , although the amount varies among species and individuals. It is extracted from sweet or sour whey. The name comes from or , the Latin word for milk,...
, the repressor changes conformation and falls off the operator and RNAP is able to bind to the promoter. Lactose is called an inducer because it inactivates the repressor and induces transcription.
See also
- Promoter (biology)
- Activator (genetics)Activator (genetics)An activator is a DNA-binding protein that regulates one or more genes by increasing the rate of transcription. The activator may increase transcription by virtue of a connected domain which assists in the formation of the RNA polymerase holoenzyme, or may operate through a coactivator. A...
- OperonOperonIn genetics, an operon is a functioning unit of genomic DNA containing a cluster of genes under the control of a single regulatory signal or promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo trans-splicing to create...
- Regulation of gene expressionRegulation of gene expressionGene modulation redirects here. For information on therapeutic regulation of gene expression, see therapeutic gene modulation.Regulation of gene expression includes the processes that cells and viruses use to regulate the way that the information in genes is turned into gene products...
- Transcription factorTranscription factorIn molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
- lac repressorLac repressorThe lac repressor is a DNA-binding protein which inhibits the expression of genes coding for proteins involved in the metabolism of lactose in bacteria. These genes are repressed when lactose is not available to the cell, ensuring that the bacterium only invests energy in the production of...
- P300/CBPP300/CBPThe p300-CBP coactivator family is composed of two closely related transcriptional co-activating proteins :#p300 # CBP...
- Glossary of gene expression termsGlossary of gene expression termsSee also: gene expression, List of Glossaries, List of Natural Sciences Glossaries-A:*Activator - protein that binds to an enhancer and activates transcription from nearby promoter....