Allovalency revisited: An analysis of multisite phosphorylation and substrate rebinding
Allovalency revisited: An analysis of multisite phosphorylation and substrate rebinding
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DOI：
10.1063/1.2841124
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发表时间：
2008-03-21
影响因子：
4.4
通讯作者：
Locasale, Jason W.
中科院分区：
文献类型：
--
作者：
Locasale, Jason W.
利用多个磷酸化位点调节生物反应在细胞信号传导中是普遍存在的。如果每个位点都贡献了一个额外的、等价的结合位点，那么磷酸化数量增加的一个结果可能是增加了配体在解离后立即与其受体重新结合的概率。这些效应如何影响细胞信号系统尚不清楚。在这里，一个自洽的积分方程形式主义配体结合，结合蒙特卡罗模拟，进一步研究多个，等效的结合位点上塑造的生物反应的影响。多个制度，定性不同的物理特性，由于不同的流行率的再结合效应的预测。计算表明，当配体再结合的剂量响应显着贡献，一个纯粹的等价模型可以影响结合曲线非线性。该模型还预测，配体重新结合本身似乎不足以产生高度合作的生物反应。(c)2008年美国物理学会。
The utilization of multiple phosphorylation sites in regulating a biological response is ubiquitous in cell signaling. If each site contributes an additional, equivalent binding site, then one consequence of an increase in the number of phosphorylations may be to increase the probability that, upon dissociation, a ligand immediately rebinds to its receptor. How such effects may influence cell signaling systems is not well understood. Here, a self-consistent integral equation formalism for ligand rebinding, in conjunction with Monte Carlo simulations, is employed to further investigate the effects of multiple, equivalent binding sites on shaping biological responses. Multiple regimes that characterize qualitatively different physics due to the differential prevalence of rebinding effects are predicted. Calculations suggest that when ligand rebinding contributes significantly to the dose response, a purely allovalent model can influence the binding curves nonlinearly. The model also predicts that ligand rebinding in itself appears insufficient to generate a highly cooperative biological response. (c) 2008 American Institute of Physics.