Daber Robert, Sharp Kim, Lewis Mitchell
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, 37th and Hamilton Walk, Philadelphia, PA 19104-6059, USA.
J Mol Biol. 2009 Oct 9;392(5):1133-44. doi: 10.1016/j.jmb.2009.07.050. Epub 2009 Jul 22.
In both prokaryotic and eukaryotic organisms, repressors and activators are responsible for regulating gene expression. The lac operon is a paradigm for understanding how metabolites function as signaling molecules and modulate transcription. These metabolites or allosteric effector molecules bind to the repressor and alter the conformational equilibrium between the induced and the repressed states. Here, we describe a set of experiments where we modified a single inducer binding site in a dimeric repressor and examined its effect on induction. Based upon these observations, we have been able to calculate the thermodynamic parameters that are responsible for the allosteric properties that govern repressor function. Understanding how effector molecules alter the thermodynamic properties of the repressor is essential for establishing a detailed understanding of gene regulation.
在原核生物和真核生物中,阻遏物和激活物都负责调节基因表达。乳糖操纵子是理解代谢物如何作为信号分子发挥作用并调节转录的范例。这些代谢物或别构效应分子与阻遏物结合,改变诱导态和阻遏态之间的构象平衡。在此,我们描述了一组实验,其中我们在二聚体阻遏物中修饰了一个单一的诱导物结合位点,并研究了其对诱导的影响。基于这些观察结果,我们能够计算出负责控制阻遏物功能的别构特性的热力学参数。理解效应分子如何改变阻遏物的热力学特性对于深入了解基因调控至关重要。