Tryptophan repressor
Encyclopedia
Tryptophan repressor is a transcription factor
involved in controlling amino acid
metabolism. It has been best studied in Escherichia coli
, where it is a dimeric protein that regulates transcription of the 5 genes in the tryptophan operon
. When the amino acid tryptophan
is plentiful in the cell, it binds to the protein, which causes a conformational change in the protein. The repressor complex then binds to its operator sequence in the 5 genes it regulates, shutting off the genes.
One of these genes, trpR, codes for the production of tryptophan itself. Another codes for the tryptophan repressor protein. These are forms of feedback regulation
.
The (tryptophan) repressor is a 25 kD protein
which regulates transcription
of the tryptophan
biosynthetic pathway in bacteria
. There are 5 operons which are regulated by trpR: the trpEDCBA, trpR, AroH, AroL, and mtr operons.
tryptophan is in plentiful supply in the cell, trpR binds 2 molecules of tryptophan, which alters its structure and dynamics so that it becomes able to bind to operator DNA
. When this occurs, transcription of the DNA is prevented, suppressing the products of the gene - proteins which make more tryptophan. When the cellular levels of tryptophan decline, the tryptophan molecules on the repressor fall off, allowing the repressor to return to its inactive form.
trpR also controls the regulation of its own production, through regulation of the trpR gene.
The structure of the ligand
-bound holorepressor, and the ligand-free forms have been determined by both X-ray crystallography
and NMR.
The trp operon consists of a regulatory gene, a promoter, an operator, and a terminator. The trp operon is active only when cellular tryptophan is scarce. If there isn't enough tryptophan, the repressor protein breaks off from the operator (where the repressor is normally bound) and RNA polymerase
can complete its reading of the strand of DNA. If the RNA polymerase reaches the terminator (at the end of the DNA strand), the enzyme for tryptophan is made.
Transcription factor
In 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...
involved in controlling amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
metabolism. It has been best studied in 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...
, where it is a dimeric protein that regulates transcription of the 5 genes in the tryptophan operon
Operon
In 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...
. When the amino acid tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
is plentiful in the cell, it binds to the protein, which causes a conformational change in the protein. The repressor complex then binds to its operator sequence in the 5 genes it regulates, shutting off the genes.
One of these genes, trpR, codes for the production of tryptophan itself. Another codes for the tryptophan repressor protein. These are forms of feedback regulation
Negative feedback
Negative feedback occurs when the output of a system acts to oppose changes to the input of the system, with the result that the changes are attenuated. If the overall feedback of the system is negative, then the system will tend to be stable.- Overview :...
.
The (tryptophan) repressor is a 25 kD protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
which regulates 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 tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
biosynthetic pathway in bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
. There are 5 operons which are regulated by trpR: the trpEDCBA, trpR, AroH, AroL, and mtr operons.
Mechanism
When the amino acidAmino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
tryptophan is in plentiful supply in the cell, trpR binds 2 molecules of tryptophan, which alters its structure and dynamics so that it becomes able to bind to operator 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...
. When this occurs, transcription of the DNA is prevented, suppressing the products of the gene - proteins which make more tryptophan. When the cellular levels of tryptophan decline, the tryptophan molecules on the repressor fall off, allowing the repressor to return to its inactive form.
trpR also controls the regulation of its own production, through regulation of the trpR gene.
The structure of the ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
-bound holorepressor, and the ligand-free forms have been determined by both X-ray crystallography
X-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...
and NMR.
The trp operon consists of a regulatory gene, a promoter, an operator, and a terminator. The trp operon is active only when cellular tryptophan is scarce. If there isn't enough tryptophan, the repressor protein breaks off from the operator (where the repressor is normally bound) and 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...
can complete its reading of the strand of DNA. If the RNA polymerase reaches the terminator (at the end of the DNA strand), the enzyme for tryptophan is made.