Heightened sensitivity of a lattice of membrane receptors
Heightened sensitivity of a lattice of membrane receptors
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DOI：
10.1073/pnas.96.18.10104
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发表时间：
1999-08-31
影响因子：
11.1
通讯作者：
Bray, D
中科院分区：
文献类型：
--
作者：
Duke, TAJ;Bray, D
真核细胞和原核细胞中的受体蛋白已被发现在质膜上形成二维簇。在这项研究中，我们研究的命题，这样的集群可能会显示协调的反应，因为从一个受体的构象状态的传播到它的邻居。开发了一种Monte Carlo模拟，其中受体以概率方式在活性和非活性状态之间翻转。构象能取决于（i）配体结合，（ii）受体的化学修饰赋予适应，和（iii）相邻受体的活性。速率常数是基于已知的生物受体，特别是细菌焦油受体的数据，并从一个类似的伊辛模型的理论约束。模拟系统显示出一个大大增强的灵敏度与相应的一组未偶联受体相比，外部信号，并在更广泛的环境浓度范围内的操作。这些和其他性质应该使构象偶联受体的晶格理想地适合作为细胞可以检测和响应细胞外刺激的“鼻子”。
Receptor proteins in both eukaryotic and prokaryotic cells have been found to form two-dimensional clusters in the plasma membrane. In this study, we examine the proposition that such clusters might show coordinated responses because of the spread of conformational states from one receptor to its neighbors. A Monte Carlo simulation was developed in which receptors flipped in probabilistic fashion between an active and an inactive state. Conformational energies depended on (i) ligand binding, (ii) a chemical modification of the receptor conferring adaptation, and (iii) the activity of neighboring receptors. Rate constants were based on data from known biological receptors, especially the bacterial Tar receptor, and on theoretical constraints derived from an analogous Ising model. The simulated system showed a greatly enhanced sensitivity to external signals compared with a corresponding set of uncoupled receptors and was operational over a much wider range of ambient concentrations. These and other properties should make a lattice of conformationally coupled receptors ideally suited to act as a "nose" by which a cell can detect and respond to extracellular stimuli.