Lac repressor

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Lac repressor

] The lac repressor is a DNA-binding protein which inhibits the expression
Gene expression

Gene expression is the process by which inheritable information from a gene, such as the DNA sequence, is made into a functional gene product, such as protein or RNA....
of gene
Gene

A gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cell and pass genetic trait to offspring....
s coding for proteins involved in the metabolism
Metabolism

Metabolism is the set of chemical reactions that occur in living organisms in order to maintain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments....
of lactose
Lactose

Lactose is a sugar that is found most notably in milk. Lactose makes up around 2?8% of milk . The name comes from the Latin word for milk, plus the -ose ending used to name sugars....
in bacteria. It is active in the absence of lactose
Lactose

Lactose is a sugar that is found most notably in milk. Lactose makes up around 2?8% of milk . The name comes from the Latin word for milk, plus the -ose ending used to name sugars....
, ensuring that the bacterium only invests energy in the production of machinery necessary for the uptake and metabolism of lactose when lactose is present. When lactose becomes available, it is converted into allolactose
Allolactose

Allolactose is a disaccharide similar to lactose. It consists of the monosaccharides ?-D-galactose and ?-D-glucose linked through a ?1-6 glycosidic linkage....
, which inhibits the lac repressor's DNA binding ability.

lac repressor (LacI) operates by binding to the major groove of the operator region of 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, a promoter, a terminator , and an operator ....
.

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] The lac repressor is a DNA-binding protein which inhibits the expression
Gene expression

Gene expression is the process by which inheritable information from a gene, such as the DNA sequence, is made into a functional gene product, such as protein or RNA....
of gene
Gene

A gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cell and pass genetic trait to offspring....
s coding for proteins involved in the metabolism
Metabolism

Metabolism is the set of chemical reactions that occur in living organisms in order to maintain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments....
of lactose
Lactose

Lactose is a sugar that is found most notably in milk. Lactose makes up around 2?8% of milk . The name comes from the Latin word for milk, plus the -ose ending used to name sugars....
in bacteria. It is active in the absence of lactose
Lactose

Lactose is a sugar that is found most notably in milk. Lactose makes up around 2?8% of milk . The name comes from the Latin word for milk, plus the -ose ending used to name sugars....
, ensuring that the bacterium only invests energy in the production of machinery necessary for the uptake and metabolism of lactose when lactose is present. When lactose becomes available, it is converted into allolactose
Allolactose

Allolactose is a disaccharide similar to lactose. It consists of the monosaccharides ?-D-galactose and ?-D-glucose linked through a ?1-6 glycosidic linkage....
, which inhibits the lac repressor's DNA binding ability.

Function
The lac repressor (LacI) operates by binding to the major groove of the operator region of 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, a promoter, a terminator , and an operator ....
. This blocks RNA polymerase from binding, and so prevents transcription
Transcription (genetics)

Transcription is the synthesis of RNA under the direction of DNA. RNA synthesis, or transcription, is the process of transcribing DNA nucleotide sequence information into RNA sequence information....
of the mRNA coding for the Lac proteins. When lactose is present, allolactose binds to the lac repressor, causing an allosteric change in its shape. In its changed state, the lac repressor is unable to bind to its cognate operator.

An astute observer might wonder how allolactose could bind LacI if the genes necessary for the conversion of lactose to allolactose are under the control of the lac promoter. It turns out that the number of repressor molecules in a bacterium is low enough that at any given time, some percentage of the cells will not have enough to inhibit transcription. This is an example of biological noise. Given time, more cells in a culture will transiently have no LacI inhibition and will express the lac operon, temporarily conferring the ability to take up lactose and convert it into allolactose. This allolactose binds LacI, increasing the probability of more transcripts being made. This positive feedback loop allows for a small signal (cytoplasmic allolactose concentration) to be amplified and induce a significant change in the cell's gene expression profile. This induced state is epigenetic and somewhat heritable: in cell division, each daughter cell will likely have enough inducer to bind and deactivate LacI.

Structure
The structure of the lac repressor protein consists of three distinct regions:
a core region (which binds allolactose)
a tetramerization region (which joins four monomers in an alpha-helix bundle)
a DNA-binding region (in which two LacI proteins bind a single operator site)

The lac repressor occurs as a tetramer
Tetramer

A tetramer is a protein with four subunits . There are homo-tetramers such as glutathione S-transferase or single-strand binding protein, dimers of hetero-dimers such as haemoglobin , and hetero-tetramers, where each subunit is different....
(four identical subunits bound together). This can be viewed as two dimer
Dimer

File:Carboxylic acid dimers.pngA dimer is a chemical or biological entity consisting of two identical subunits called monomers, which are held together by either intramolecular forces or weaker intermolecular forces....
s, with each dimer being able to bind to a single lac operator. The two subunits each bind to a slightly separated (major groove) region of the operator. The promoter is slightly covered by the lac repressor so RNAP cannot bind to and transcribe the operon.

The DNA binding region consists of a helix-turn-helix
Helix-turn-helix

In proteins, the helix-turn-helix is a major structural motif capable of binding DNA. It is composed of two alpha helix joined by a short strand of amino acids and is found in many proteins that regulate gene expression....
structural motif
Structural motif

In an unbranched, polymer biological molecule, such as a protein or a strand of RNA, a structural motif is a three-dimensional structural element or protein folding within the chain, which appears also in a variety of other molecules....
.

Interactive, rotating 3D views of the repressor structure, some bound to DNA, including morphs of how it bends the DNA double helix, are available at .

Discovery
The lac repressor was first isolated
Protein purification

Protein purification is a series of processes intended to isolate a single type of protein from a complex mixture. Protein purification is vital for the characterisation of the function, structure and interactions of the protein of interest....
by Walter Gilbert
Walter Gilbert

Walter Gilbert is an United States Physics, Biochemistry, molecular biology pioneer, and Nobel laureate....
and Beno Müller-Hill in 1966. They were able to show, in vitro
In vitro

In vitro refers to the technique of performing a given procedure in a controlled environment outside of a living organism. Some may argue that in vitro refers to a process that is created in a "test tube"; however, Robert Kail and John Cavanaugh on page 58 in the 4th edition of Human Development: A Life-Span View cite that in fact th...
, that the protein bound to DNA containing the lac operon, and released the DNA when IPTG
IPTG

Isopropyl ?-D-1-thiogalactopyranoside, abbreviated IPTG, is a molecular biology reagent.This compound is used as a molecular mimic of allolactose, a lactose metabolite that triggers Transcription of the lac operon....
was added. (IPTG is an allolactose analog
Analog (chemistry)

In chemistry, analogs or analogues are chemical compound in which one or more individual atoms have been replaced, either with a different atom, or with a different functional group....
.) They were also able to isolate the portion of DNA bound by the protein by using the enzyme
Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
deoxyribonuclease
Deoxyribonuclease

A deoxyribonuclease is any enzyme that catalyzes the hydrolysis of phosphodiester bonds in the DNA backbone. Deoxyribonucleases are thus one type of nuclease....
, which breaks down DNA. After treatment of the repressor-DNA complex, some DNA remained, suggesting that it had been masked by the repressor. This was later confirmed.

These experiments were important, as they confirmed the mechanism of the lac operon, earlier proposed by Jacques Monod
Jacques Monod

See also Jacques-Louis Monod, French-born composer and cousin of Jacques Monod.Jacques Lucien Monod was a French biology who was awarded a Nobel Prize in Physiology or Medicine in 1965....
and Francois Jacob
François Jacob

Fran?ois Jacob is a France biologist who, together with Jacques Monod, originated the idea that control of enzyme levels in all cell s occurs through feedback on Transcription ....
.

External links

See also

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, a promoter, a terminator , and an operator ....