Conformational spread in a ring of proteins:: A stochastic approach to allostery
Conformational spread in a ring of proteins:: A stochastic approach to allostery
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DOI：
10.1006/jmbi.2001.4610
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发表时间：
2001-05-04
影响因子：
5.6
通讯作者：
Bray, D
中科院分区：
文献类型：
--
作者：
Duke, TAJ;Le Novère, N;Bray, D
我们最近提出，细菌中一簇膜受体的敏感性和范围将通过邻近蛋白质之间的合作相互作用而增强。在这里，我们研究了这种“构象扩散”机制对一个理想的一维系统的影响，该系统包括一个由相同变构原体（蛋白质分子或一组作为一个单位运作的蛋白质结构域）组成的闭合环。我们通过分析和蒙特卡罗模拟表明，变构原体环可以对配体浓度的变化表现出类似开关的响应。导出了开关灵敏度和协同性的表达式，并证明了最大灵敏度与环中原聚体的数目成正比。这种环可以重现细菌鞭毛马达开关复合物的敏感性和动力学，例如，它是基于34个FliM蛋白的环。我们还比较了构象偶联原聚物与经典变构蛋白（如血红蛋白）的较小环，并表明典型的MWC和KNF模型作为限制情况自然出现。构象扩散似乎是我们熟悉的变构机制的自然延伸：一种物理上现实的机制，应该广泛适用于许多由蛋白质分子构建的结构。(C) 2001学术出版社。
We recently suggested that the sensitivity and range of a cluster of membrane receptors in bacteria would be enhanced by cooperative interactions between neighbouring proteins. Here, we examine the consequences of this "conformational spread" mechanism for an idealised one-dimensional system comprising a closed ring of identical allosteric protomers (protein molecules, or a group of protein domains operating as a unit). We show analytically and by means of Monte Carlo simulations that a ring of allosteric protomers can exhibit a switch-like response to changes in ligand concentration. We derive expressions for the sensitivity and cooperativity of switching and show that the maximum sensitivity is proportional to the number of protomers in the ring. A ring of this kind can reproduce the sensitivity and kinetics of the switch complex of a bacterial flagellar motor, for example, which is based on a ring of 34 FliM proteins. We also compare smaller rings of conformationally coupled protomers to classical allosteric proteins such as haemoglobin and show that the canonical MWC and KNF models arise naturally as limiting cases. Conformational spread appears to be a natural extension of the familiar mechanism of allostery: a physically realistic mechanism that should apply widely to many structures built from protein molecules. (C) 2001 Academic Press.