Effect of lac repressor oligomerization on regulatory outcome.
Effect of lac repressor oligomerization on regulatory outcome.
复制标题
lac 阻遏物寡聚化对调节结果的影响。
DOI：
10.1111/j.1365-2958.1992.tb02162.x
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发表时间：
1992
影响因子：
3.6
通讯作者：
Matthews,KS
中科院分区：
文献类型：
--
作者：
Chakerian,AE;Matthews,KS
细菌操纵子的调控结果取决于影响信使核糖核酸产生的所有成分之间的相互作用。MRNA水平可以被调节转录启动的负性和正性调控元件深刻地改变。抑制子和激活子对DNA上调控位点的占据不仅取决于这些蛋白质对其同源位点的亲和力(S)，还取决于调控蛋白的寡聚体状态。大肠杆菌中的操纵子为蛋白质组装对相关结构基因转录状态的影响提供了一个很好的原型例子。DNA环的形成对于最大限度地抑制操纵子是必不可少的，它取决于DNA中是否存在多个操纵子位点，以及抑制子自结合形成双齿四聚体的能力。这种环状复合体的稳定性通过DNA超螺旋而显著增强。由二聚体组装而成的四聚体显然是通过蛋白质C-末端结构域中的亮氨酸拉链基序的相互作用而发生的，而四聚体是形成环状复合体所必需的。此外，对二聚体突变体的DNA结合特性的分析表明，单体-二聚体结合和二聚体-DNA结合(单体不与DNA结合)是耦合平衡。因此，二聚体组装是产生DNA结合单位所必需的，而四聚体组装是形成稳定的环状DNA结构所必需的，它最大限度地抑制了mRNA的合成。因此，蛋白质-蛋白质相互作用在抑制物的调节活动中起着关键作用，在分析任何寡聚DNA结合蛋白的活性时都必须加以考虑。
Regulatory outcome in a bacterial operon depends on the interactions of all the components which influence mRNA production. Levels of mRNA can be altered profoundly by both negative and positive regulatory elements which modulate initiation of transcription. The occupancy of regulatory sites on the DNA by repressors and activators is determined not only by the affinity of these proteins for their cognate site(s) but also by the oligomeric state of the regulatory protein. Thelacoperon inEscherichia coliprovides an excellent prototypic example of the influence of protein assembly on the transcriptional status of the associated structural genes. DNA loop formation is essential for maximal repression of thelacoperon and is contingent upon the presence of multiple operator sites in the DNA and the ability of the repressor to self‐associate to form a bidentate tetramer. The stability of this looped complex is enhanced significantly by DNA supercoiling. Tetramer assembly from dimers apparently occurs via interactions of a‘leucine zipper’motif in the C‐terminal domain of the protein, and the tetramer is essential to formation of looped complexes. Furthermore, analysis of the DNA‐binding characteristics of dimeric mutants has established that the monomer‐dimer association and dimer‐DNA binding (monomer does not bind to DNA) are coupled equilibria. Thus, dimer assembly is essential for generating a DNA‐binding unit, and tetramer assembly is required for formation of the stable looped DNA structure that maximally represses mRNA synthesis. Protein‐protein interactions therefore play a pivotal role in the regulatory activities of thelacrepressor and must be considered when analysing the activities of any oligomeric DNA‐binding protein.