Information theoretical quantification of cooperativity in signalling complexes
Information theoretical quantification of cooperativity in signalling complexes
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DOI：
10.1186/1752-0509-3-9
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发表时间：
2009-01-16
影响因子：
--
通讯作者：
Rousseau, Frederic
中科院分区：
文献类型：
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作者：
Lenaerts, Tom;Ferkinghoff-Borg, Jesper;Rousseau, Frederic
背景：细胞内信息交换是由相互作用的信号蛋白级联推动的，对细胞的正常功能和存活至关重要。现在，几种生物的相互作用正在被绘制，蛋白质分子水平上合作的几种结构机制已经被阐明，在这些非常多样化的生物环境中，这种基本数量的形式化，即信息，变得可行。结果：我们在这里表明香农互信息量化了生物系统中的信息，更具体地说，是大分子复合物组装所固有的协同性。我们展示了蛋白质复合物如何被视为噪声通信通道的特定实例。我们进一步展示，使用p27调控途径的一部分，如何使用经典平衡热力学量（如结合亲和力和化学势）来量化信息交换，同时也确定工程特性（如通道噪声和通道容量）。因此，这种信息测量识别和量化那些蛋白质浓度，使生化系统在细胞内过程的活性和非活性状态之间最有效地转换。结论：本文提出的框架为分析协同性对大分子复合物组装的影响提供了一种新颖的方法。它显示了由蛋白质浓度提供的特定系统最有效地发挥作用的条件，即交换最多的信息。因此，这个框架开启了直接从系统敏感性、稳健性或可塑性对信息交换的影响方面把握生物品质的可能性。虽然这些参数也可以使用经典热力学参数推导出来，但从信息交换的角度对生物信号进行重铸，为可视化网络合作提供了另一种框架，在某些情况下可能更直观。
Background: Intra-cellular information exchange, propelled by cascades of interacting signalling proteins, is essential for the proper functioning and survival of cells. Now that the interactome of several organisms is being mapped and several structural mechanisms of cooperativity at the molecular level in proteins have been elucidated, the formalization of this fundamental quantity, i.e. information, in these very diverse biological contexts becomes feasible.Results: We show here that Shannon's mutual information quantifies information in biological system and more specifically the cooperativity inherent to the assembly of macromolecular complexes. We show how protein complexes can be considered as particular instances of noisy communication channels. Further we show, using a portion of the p27 regulatory pathway, how classical equilibrium thermodynamic quantities such as binding affinities and chemical potentials can be used to quantify information exchange but also to determine engineering properties such as channel noise and channel capacity. As such, this information measure identifies and quantifies those protein concentrations that render the biochemical system most effective in switching between the active and inactive state of the intracellular process.Conclusion: The proposed framework provides a new and original approach to analyse the effects of cooperativity in the assembly of macromolecular complexes. It shows the conditions, provided by the protein concentrations, for which a particular system acts most effectively, i.e. exchanges the most information. As such this framework opens the possibility of grasping biological qualities such as system sensitivity, robustness or plasticity directly in terms of their effect on information exchange. Although these parameters might also be derived using classical thermodynamic parameters, a recasting of biological signalling in terms of information exchange offers an alternative framework for visualising network cooperativity that might in some cases be more intuitive.