Allostery in oligomeric receptor models

Allostery in oligomeric receptor models
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寡聚受体模型中的变构

DOI:
10.1093/imammb/dqz016
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发表时间:
2019
期刊:
Mathematical Medicine and Biology: A Journal of the IMA
影响因子:
--
通讯作者:
Conradi Smith, Gregory Douglas
Conradi Smith, Gregory Douglas
中科院分区:
--
文献类型:
--
作者:
Conradi Smith, Gregory Douglas

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我们展示了如何受体同源二聚体的平衡结合曲线可以表示为合理的多项式函数的组成单体的平衡结合曲线,没有近似和不假设独立的受体单体。使用一个独特的生成树结构,减少图形的权力,该方法适当占受体单体之间的热力学约束和变构相互作用(即构象偶联)。该方法是完全通用的,它开始于一个任意的无向图表示的单体状态转换图的拓扑结构,并结束于由两个或多个相同的和不可区分的单体组成的受体寡聚体的平衡结合曲线的代数表达式。分析了几个具体的例子,包括鸟嘌呤核苷酸结合蛋白偶联受体二聚体和四聚体组成的多个“三元复合物”单体。
We show how equilibrium binding curves of receptor homodimers can be expressed as rational polynomial functions of the equilibrium binding curves of the constituent monomers, without approximation and without assuming independence of receptor monomers. Using a distinguished spanning tree construction for reduced graph powers, the method properly accounts for thermodynamic constraints and allosteric interactions between receptor monomers (i.e. conformational coupling). The method is completely general; it begins with an arbitrary undirected graph representing the topology of a monomer state-transition diagram and ends with an algebraic expression for the equilibrium binding curve of a receptor oligomer composed of two or more identical and indistinguishable monomers. Several specific examples are analysed, including guanine nucleotide-binding protein-coupled receptor dimers and tetramers composed of multiple ‘ternary complex’ monomers.
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