Structural analysis of the genetic switch that regulates the expression of restriction-modification genes.

Structural analysis of the genetic switch that regulates the expression of restriction-modification genes.
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调节限制性修饰基因表达的遗传开关的结构分析。

DOI:
10.1093/nar/gkn448
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发表时间:
2008-08
影响因子:
14.9
通讯作者:
Kneale GG
Kneale GG
中科院分区:
生物学2区
文献类型:
--
作者:
McGeehan JE;Streeter SD;Thresh SJ;Ball N;Ravelli RB;Kneale GG

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控制蛋白(C)通过正反馈和负反馈回路的组合来调节限制和修饰(R-M)基因表达的时间。与操纵基因结合的单个二聚体开启C基因和核酸内切酶基因的转录;在更高的浓度下,第二个二聚体相邻地关闭这些基因。在这里,我们报告的第一个结构的C蛋白-DNA操作符复合物,由两个C蛋白二聚体结合到本地35 bp的操作序列的R-M系统Esp 1396 I。该结构揭示了直接和间接DNA序列识别的作用。复合物中的DNA结构高度扭曲,小沟的严重压缩导致每个操纵基因位点内的50°弯曲,以及DNA序列中心的大沟的大幅扩展。二聚体之间的合作结合管理的浓度依赖性激活抑制开关,并产生,部分地,从Glu 25和Arg 35侧链在二聚体-二聚体界面的相互作用。Arg 35和RNA聚合酶σ70亚基的一个等价残基之间竞争Glu 25位点,支持核酸内切酶基因从激活到抑制的转变。
Controller (C) proteins regulate the timing of the expression of restriction and modification (R–M) genes through a combination of positive and negative feedback circuits. A single dimer bound to the operator switches on transcription of the C-gene and the endonuclease gene; at higher concentrations, a second dimer bound adjacently switches off these genes. Here we report the first structure of a C protein–DNA operator complex, consisting of two C protein dimers bound to the native 35 bp operator sequence of the R–M system Esp1396I. The structure reveals a role for both direct and indirect DNA sequence recognition. The structure of the DNA in the complex is highly distorted, with severe compression of the minor groove resulting in a 50° bend within each operator site, together with a large expansion of the major groove in the centre of the DNA sequence. Cooperative binding between dimers governs the concentration-dependent activation–repression switch and arises, in part, from the interaction of Glu25 and Arg35 side chains at the dimer–dimer interface. Competition between Arg35 and an equivalent residue of the σ70 subunit of RNA polymerase for the Glu25 site underpins the switch from activation to repression of the endonuclease gene.
DOI: 10.1107/s0907444904019158
发表时间: 2004-12-01
影响因子: 2.2
作者:
Emsley, P;Cowtan, K
通讯作者: Cowtan, K
DOI: 10.1080/07391102.1988.10506483
发表时间: 1988-08-01
影响因子: 4.4
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LAVERY, R;SKLENAR, H
通讯作者: SKLENAR, H
DOI: 10.1107/s0907444994003112
发表时间: 1994-09-01
期刊: ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子: --
作者:
BAILEY, S
通讯作者: BAILEY, S
DOI: 10.1093/nar/26.8.1906
发表时间: 1998-04-15
影响因子: 14.9
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Dickerson, RE
通讯作者: Dickerson, RE
DOI: 10.1016/j.jmb.2004.12.025
发表时间: 2005-02-25
影响因子: 5.6
作者:
McGeehan, JE;Streeter, SD;Kneale, GG
通讯作者: Kneale, GG