An allosteric model for heterogeneous receptor complexes: Understanding bacterial chemotaxis responses to multiple stimuli

An allosteric model for heterogeneous receptor complexes: Understanding bacterial chemotaxis responses to multiple stimuli
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DOI:
10.1073/pnas.0506961102
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发表时间:
2005-11-29
影响因子:
11.1
通讯作者:
Tu, YH
Tu, YH
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Mello, BA;Tu, YH

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本文将经典的Monod-Wyman-Changeux模型推广到均相变构蛋白复合体,用来模拟异质受体复合体对多种配体刺激的反应。我们表明,最近的体内实验数据表明,具有不同化学受体表达水平的突变菌株对不同类型的刺激的趋化反应[Sourjik,V.&Berg,H.C.(2004)Natural 428,437-441]都可以在这个广义的Monod-Wyman-Changeux模型中一致解释。基于模型和现有数据,定量预测了所有菌株(本文研究的)对任何配体(Ser和MeAsp)浓度组合的响应,以供未来的实验验证。通过对体内反应数据的模拟,我们的研究揭示了关于不同类型的单个受体的属性以及簇的组成的重要信息。还讨论了簇的非配体结合、细胞质部分,如CHEA和CHEW的能量贡献。广义变构模型为理解细菌趋化中的信号整合和分化提供了一致的框架。这对研究其他多相受体复合体的功能也是有用的。
The classical Monod-Wyman-Changeux model for homogeneous allosteric protein complex is generalized in this article to model the responses of heterogeneous receptor complexes to multiple types of ligand stimulus. We show that the recent in vivo experimental data of Escherichia coli chemotaxis responses for mutant strains with different expression levels of the chemo-receptors to different types of stimulus [Sourjik, V. & Berg, H. C. (2004) Nature 428, 437-441] all can be explained consistently within this generalized Monod-Wyman-Changeux model. Based on the model and the existing data, responses of all of the strains (studied in this article) to the presence of any combinations of ligand (Ser and MeAsp) concentrations are predicted quantitatively for future experimental verification. Through modeling the in vivo response data, our study reveals important information about the properties of different types of individual receptors, as well as the composition of the cluster. The energetic contribution of the nonligand binding, cytoplasmic parts of the cluster, such as CheA and CheW, is also discussed. The generalized allosteric model provides a consistent framework in understanding signal integration and differentiation in bacterial chemotaxis. it should also be useful for studying the functions of other heterogeneous receptor complexes.