Lac Repressor molecule more details...

The lac repressor is a DNA-binding protein which inhibits the expression of genes coding for proteins involved in the metabolism of lactose in bacteria. It is active in the absence of lactose, 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, which inhibits the lac repressor's DNA binding ability. Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ... Gene expression, or simply expression, is the process by which the inheritable information which comprises a gene, such as the DNA sequence, is made manifest as a physical and biologically functional gene product, such as protein or RNA. Several steps in the gene expression process may be modulated, including the... For other uses, see Gene (disambiguation). ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... A few of the metabolic pathways in a cell. ... Lactose is a disaccharide that consists of β-D-galactose and β-D-glucose molecules bonded through a β1-4 glycosidic linkage. ... Lactose is a disaccharide that consists of β-D-galactose and β-D-glucose molecules bonded through a β1-4 glycosidic linkage. ... In biology, allolactose is an important isomer of lactose, a disaccharide made up of galactose and glucose. ...

Function

The lac repressor (LacI) operates by binding to the major groove of the operator region of the lac operon. This blocks RNA polymerase from binding, and so prevents transcription 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. The lac operon is an operon required for the transport and metabolism of lactose in Escherichia coli and some other enteric bacteria. ... A micrograph of ongoing gene transcription of ribosomal RNA illustrating the growing primary transcripts. ... The interaction of mRNA in a eukaryote cell. ... In biochemistry, an enzyme or other protein is allosteric if its activity or efficiency changes in response to the binding of an effector molecule at a so-called allosteric site. ...

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 LacI 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. Epigenetic inheritance is the transmission of information from a cell or multicellular organism to its descendants without that information being encoded in the nucleotide sequence of the gene. ...

Structure of a tetramer of LacI, with each monomer bound to a region of the lac promoter DNA (Determined by X-ray crystallography)

Crystal structure of lac repressor (laci) protein bound to DNA. Source: Created by Rich0. ... Crystal structure of lac repressor (laci) protein bound to DNA. Source: Created by Rich0. ... X-ray crystallography, also known as single-crystal X-ray diffraction, is the oldest and most common crystallographic method for determining the structure of molecules. ...

Structure

The lac repressor protein has 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 (four identical subunits bound together). This can be viewed as two dimers, 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. A tetramer is a protein with four subunits (tetrameric). ... Sucrose, or common table sugar, is composed of glucose and fructose. ...

The DNA binding region consists of a helix-turn-helix structural motif. The λ repressor of bacteriophage lambda employs a helix-turn-helix to bind DNA. In proteins, the helix-turn-helix (HTH) is a major structural motif capable of binding DNA. It is composed of two α helices joined by a short strand of amino acids and is found in many... In an unbranched, chain-like biological molecule, such as a protein or a strand of RNA, a structural motif is a three-dimensional structural element or fold within the chain, which appears also in a variety of other molecules. ...

Discovery

The lac repressor was first isolated by Walter Gilbert and Beno Müller-Hill in 1966^[1]. They were able to show, in vitro, that the protein bound to DNA containing the lac operon, and released the DNA when IPTG was added. (IPTG is an allolactose analog.) They were also able to isolate the portion of DNA bound by the protein by using the enzyme deoxyribonuclease, 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. Protein purification is the process of isolating proteins from a homogenate, which may comprise cell and tissue components, including DNA, cell membrane and other proteins. ... Walter Gilbert Walter Gilbert (born March 21, 1932) is an American physicist, biochemist,and molecular biology pioneer. ... Year 1966 (MCMLXVI) was a common year starting on Saturday (link will display full calendar) of the 1966 Gregorian calendar. ... Wiktionary has a definition of: In vitro In vitro (Latin: within glass) means within a test tube, or, more generally, outside a living organism or cell. ... IPTG is a common abbreviation for Isopropyl β-D-1-thiogalactopyranoside, a molecular biology reagent. ... An analog is in chemistry a chemical closely related to another usually sharing the same nucleus. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... A deoxyribonuclease (DNase, for short) is any enzyme that catalyzes the hydrolytic cleavage of phosphodiester linkages in the DNA backbone. ...

These experiments were important, as they confirmed the mechanism of the lac operon, earlier proposed by Jacques Monod and Francois Jacob. Jacques Lucien Monod (February 9, 1910 – May 31, 1976) was a French biologist and a Nobel Prize Winner in Physiology or Medicine in 1965. ... François Jacob (born June 17, 1920) is a French biologist, who together with Jacques Monod, originated the idea that control of enzyme levels in all cells happens through feedback on transcription. ...

External links

• MeSH Lac+Repressors

Medical Subject Headings (MeSH) is a huge controlled vocabulary (or metadata system) for the purpose of indexing journal articles and books in the life sciences. ...

See also

• Lac operon

The lac operon is an operon required for the transport and metabolism of lactose in Escherichia coli and some other enteric bacteria. ...

References

1. ^ Gilbert, W; Müller-Hill B (Dec 1966). "Isolation of the LAC Repressor". Proc Natl Acad Sci 56 (6): 1891-1898. PMID 16591435.