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首页> 外文期刊>Journal of Theoretical Biology >A kinetic mechanism for Drosophila bicoid cooperative binding
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A kinetic mechanism for Drosophila bicoid cooperative binding

机译:果蝇双链体协同结合的动力学机制。

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The Bicoid (Bcd) protein is a concentration-dependent transcriptional activator in the embryo of Drosophila melanogaster. Bcd regulates the expression of the maternal and zygotic gene hunchback (hb) that shows a step-like-function expression pattern, in the anterior half of the egg. The regulatory region of hb contains six major binding sites for the Bed protein, named A1, A2, A3 (strong sites), and X1, X2, X3 (weak sites). Cooperativity between Bcd molecules binding to the hb enhancer element has been characterized as an important mechanism for the step-like shape of hb anterior expression domain. The objective of the present report is to analyse the mechanism of this cooperative binding based on a reaction network model. Using this method we have analysed experimental results from the literature describing how the Bcd protein binds to hb enhancer elements containing the A1 or X1 site alone or these two sites together at wild type distance. This approach allows us to estimate the kinetic constants of protein-protein and protein-DNA interactions. Moreover our results suggest that binding of a Bcd dimer to the hb enhancer element is more stable than binding of a monomer. We propose a cooperative kinetic mechanism for binding of Bcd to the hb enhancer element: First, a monomer binds to the site with a relatively low affinity; after that, another monomer binds to the first one with higher affinity, generating a dimer bound to the site. This yet unreported monomer-monomer cooperative mechanism takes place for occupancy of either one-site or two-site enhancer elements. In addition, we find cooperativity between neighbor sites, as previously reported in the literature. (c) 2005 Elsevier Ltd. All rights reserved.
机译:Bicoid(Bcd)蛋白是果蝇果蝇胚胎中浓度依赖性的转录激活因子。 Bcd调节母体和合子基因驼背(hb)在卵前半部中表现出阶梯状功能表达模式的表达。 hb的调控区包含Bed蛋白的六个主要结合位点,分别称为A1,A2,A3(强位点)和X1,X2,X3(弱位点)。 Bcd分子与hb增强子元件结合的协同性已被表征为hb前表达域呈阶梯状形状的重要机制。本报告的目的是基于反应网络模型分析这种合作绑定的机制。使用这种方法,我们分析了文献中描述Bcd蛋白如何与仅包含A1或X1位点或这两个位点的野生型距离的hb增强子结合的实验结果。这种方法使我们能够估计蛋白质-蛋白质和蛋白质-DNA相互作用的动力学常数。此外,我们的结果表明,Bcd二聚体与hb增强子的结合比单体结合更稳定。我们提出了一种将Bcd结合到hb增强子上的协同动力学机制:首先,单体以相对较低的亲和力结合到该位点。之后,另一种单体以更高的亲和力与第一个单体结合,生成一个与该位点结合的二聚体。这种尚未报道的单体-单体协同作用机理是为占据一个位点或两个位点的增强子元素而发生的。此外,我们发现邻居站点之间的合作性,如先前在文献中所报道的那样。 (c)2005 Elsevier Ltd.保留所有权利。

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