WordNet

block the action of
put down by force or intimidation; "The government quashes any attempt of an uprising"; "China keeps down her dissidents very efficiently"; "The rich landowners subjugated the peasants working the land" (同)quash, keep_down, subdue, subjugate, reduce
a small amount of liquor added to a food or beverage
resinlike substance secreted by certain lac insects; used in e.g. varnishes and sealing wax
the syllable naming the sixth (submediant) note of a major or minor scale in solmization (同)lah
edged or streaked with color; "white blossoms with purple-laced petals"
closed with a lace; "snugly laced shoes" (同)tied

PrepTutorEJDIC

〈暴動など〉‘を'抑圧する,鎮圧する / 〈感情など〉‘を'抑える / 〈不安・いやな記憶など〉‘を'抑圧する(意識しないようにすること)
〈U〉ひもで縛ること;レース飾りをつけること / 〈U〉(各種の用途の)ひも,レース,金(銀)モール / 〈U〉〈C〉《話》むち打ち / 〈U〉酒を加えること
ラック(ワニス・赤色染料の原料)
ラ(全音階の第6音)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/05/06 00:51:31」(JST)

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Annotated crystal structure of dimeric LacI. Two monomers (of four total) co-operate to bind each DNA operator sequence. Monomers (red and blue) contain DNA binding and core domains (labeled) which are connected by a linker (labeled). The C-terminal tetramerization helix is not shown. The repressor is shown in complex with operator DNA (gold) and ONPF (green), an anti-inducer ligand (i.e. a stabilizer of DNA binding)

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. These genes are repressed when lactose is not available to the cell, ensuring that the bacterium only invests energy in the production of machinery necessary for uptake and utilization of lactose when lactose is present. When lactose becomes available, it is converted into allolactose, which inhibits the lac repressor's DNA binding ability. Loss of DNA binding by the lac repressor is required for transcriptional activation of the operon.

Function

The lac repressor (LacI) operates by a helix-turn-helix motif in its DNA binding domain binding base-specifically to the major groove of the operator region of the lac operon, with base contacts also made by residues of symmetry-related alpha helices, the "hinge" helices, which bind deeply in the minor groove.^[1] This DNA binding causes the specific affinity of RNA polymerase for the promoter sequence to increase sufficiently that it cannot escape the promoter region and enter elongation, and so prevents transcription of the mRNA coding for the Lac proteins.^[2] 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 tightly to its cognate operator. This effect is referred to as induction, because it induces, rather than represses, expression of the metabolic genes. In vitro, Isopropyl β-D-1-thiogalactopyranoside (IPTG) is a commonly used allolactose mimic which can be used to induce transcription of genes being regulated by lac repressor.

Structure

Tetrameric LacI binds two operator sequences and induces DNA looping. Two dimeric LacI functional subunits (red+blue and green+orange) each bind a DNA operator sequence (labeled). These two functional subunits are coupled at the tetramerization region (labeled); thus, tetrameric LacI binds two operator sequences. This allows tetrameric LacI to induce DNA looping.

Structurally, the lac repressor protein is a homo-tetramer. The tetramer contains two DNA binding subunits composed of two monomers each (sometimes called "dimeric lac repressor"). These subunits dimerize to form a tetramer capable of binding two operator sequences. Each monomer ^[3]^[4]^[5] consists of four distinct regions:

an N-terminal DNA-binding domain (in which two LacI proteins bind a single operator site)
a regulatory domain (sometimes called the core domain, which binds allolactose, an allosteric effector molecule)
a linker that connects the DNA-binding domain with the core domain (sometimes called the hinge helix, which is important for allosteric communication^[5])
a C-terminal tetramerization region (which joins four monomers in an alpha-helix bundle)

DNA binding occurs via an N-terminal helix-turn-helix structural motif and is targeted to one of several operator DNA sequences (known as O₁, O₂ and O₃). The O₁ operator sequence slightly overlaps with the promoter, which increases the affinity of RNA polymerase for the promoter sequence such that it cannot enter elongation and remains in Abortive initiation. Additionally, because each tetramer contains two DNA-binding subunits, binding of multiple operator sequences by a single tetramer induces DNA looping.^[6]

Discovery

The lac repressor was first isolated by Walter Gilbert and Benno Müller-Hill in 1966.^[7] 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.

These experiments confirmed the mechanism of the lac operon, earlier proposed by Jacques Monod and Francois Jacob.

References

^ Schumacher, M. A.; Choi, K. Y.; Zalkin, H; Brennan, R. G. (1994). "Crystal structure of LacI member, PurR, bound to DNA: Minor groove binding by alpha helices". Science (New York, N.Y.) 266 (5186): 763–70. PMID 7973627. edit
^ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715899/
^ Goodsell, D. S. (2003). "Lac Repressor". RCSB Protein Data Bank. doi:10.2210/rcsb_pdb/mom_2003_3. edit
^ Lewis, M. (Jun 2005). "The lac repressor". Comptes rendus biologies 328 (6): 521–548. doi:10.1016/j.crvi.2005.04.004. ISSN 1631-0691. PMID 15950160. edit
^ ^a ^b Swint-Kruse, L.; Matthews, K. S. (2009). "Allostery in the LacI/GalR Family: Variations on a Theme". Current Opinion in Microbiology 12 (2): 129–137. doi:10.1016/j.mib.2009.01.009. PMC 2688824. PMID 19269243. edit
^ Oehler, S.; Eismann, E. R.; Krämer, H.; Müller-Hill, B. (1990). "The three operators of the lac operon cooperate in repression". The EMBO Journal 9 (4): 973–979. PMC 551766. PMID 2182324. edit
^ Gilbert, W; Müller-Hill B (December 1966). "ISOLATION OF THE LAC REPRESSOR". Proc. Natl. Acad. Sci. U.S.A. 56 (6): 1891–1898. doi:10.1073/pnas.56.6.1891. PMC 220206. PMID 16591435.

External links

Lac Repressors at the US National Library of Medicine Medical Subject Headings (MeSH)
More information on the lac repressor molecule on protein database
Lac Repressor in Proteopedia.

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English Journal

The natural DNA bending angle in the lac repressor headpiece-O1 operator complex is determined by protein-DNA contacts and water release.

Barr D, Vaart A.SourceDepartment of Chemistry and Biochemistry, Center for Biological Physics, Arizona State University, PO Box 871604, Tempe, AZ 85287, USA.
Physical chemistry chemical physics : PCCP.Phys Chem Chem Phys.2012 Feb 14;14(6):2070-7. Epub 2012 Jan 10.
We performed molecular dynamics simulations of the lac repressor headpiece-O1 operator complex for natural, over and underbent DNA to assess the factors that determine the natural DNA bending angle. At the natural angle, the specific and nonspecific contacts between the protein and DNA are optimized
PMID 22234444

FRET studies of a landscape of Lac repressor-mediated DNA loops.

Haeusler AR, Goodson KA, Lillian TD, Wang X, Goyal S, Perkins NC, Kahn JD.SourceDepartment of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742-2021 and Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109-2125, USA.
Nucleic acids research.Nucleic Acids Res.2012 Feb 4. [Epub ahead of print]
DNA looping mediated by the Lac repressor is an archetypal test case for modeling protein and DNA flexibility. Understanding looping is fundamental to quantitative descriptions of gene expression. Systematic analysis of LacI•DNA looping was carried out using a landscape of DNA constructs with lac
PMID 22307389

Japanese Journal

SK_<66>-his, a Novel Glycine-Rich Peptide Derived from Drosophila with Antibacterial Activity

FENG Zhiguo,LIU Huijuan,LANG Jun,LI Yanjiao,SHU Muya,CHEN Zhengwang
Bioscience, biotechnology, and biochemistry 73(3), 769-771, 2009-03-23
… SK66-his, a novel glycine-rich peptide derived from the CG13551 gene of Drosophila, was directly expressed in Escherichia coli with the help of the glucose effect of the lac repressor and efficiently purified in high yield (10.063 mg/l). …
NAID 10027539295

Artificial Control of Transgene Expression in Chlamydomonas reinhardtii Chloroplast Using the lac Regulation System from Escherichia coli(PLANT BIOTECHNOLOGY)

Kato Ko,Marui Takahiro,Kasai Seitaro,Shinmyo Astuhiko
Journal of bioscience and bioengineering 104(3), 207-213, 2007-09-25
… Here, we describe an artificial, controllable gene expression system using the lac regulation system from Escherichia coli that we constructed in the Chlamydomonas reinhardtii chloroplast. … This system consists of a controllable reporter gene expression cassette and the Lac repressor expression cassette. …
NAID 110006402612