How Do Thermophilic Proteins and Proteomes Withstand High Temperature?
How Do Thermophilic Proteins and Proteomes Withstand High Temperature?
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DOI：
10.1016/j.bpj.2011.05.059
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发表时间：
2011-07-06
影响因子：
3.4
通讯作者：
Ghosh, Kingshuk
中科院分区：
文献类型：
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作者：
Sawle, Lucas;Ghosh, Kingshuk
我们试图通过分析116种蛋白质的热力学数据（迄今为止获得的最大数据集）来了解嗜热蛋白质稳定性增强的起源。我们计算的熵和焓的变化，在收敛温度下，不同的驱动力是最大程度地解耦，在大多数以前的研究中进行的熔化温度。我们发现，平均而言，在折叠时的焓的增益是较低的嗜热菌比中温菌，而在折叠时的熵的损失是较高的中温菌比嗜热菌。这意味着熵稳定化可能是负责高熔融温度，并暗示在嗜热变性状态的残留结构或紧凑性。我们发现一个类似的趋势，通过分析一组同源的蛋白质分类的基础上，只有最佳的生长温度的生物体，他们被提取。我们发现，在最大稳定性的温度下的折叠自由能是显着更有利的嗜热菌比中温菌，而最大稳定温度本身是这两个类之间是相似的。此外，我们扩展了热力学分析模型的整个蛋白质组。结果解释了高的最佳生长温度在嗜热生物，并在良好的定量协议与充分的热生长速率数据中获得的十几个嗜热和嗜温生物。
We attempt to understand the origin of enhanced stability in thermophilic proteins by analyzing thermodynamic data for 116 proteins, the largest data set achieved to date. We compute changes in entropy and enthalpy at the convergence temperature where different driving forces are maximally decoupled, in contrast to the majority of previous studies that were performed at the melting temperature. We find, on average, that the gain in enthalpy upon folding is lower in thermophiles than in mesophiles, whereas the loss in entropy upon folding is higher in mesophiles than in thermophiles. This implies that entropic stabilization may be responsible for the high melting temperature, and hints at residual structure or compactness of the denatured state in thermophiles. We find a similar trend by analyzing a homologous set of proteins classified based only on the optimum growth temperature of the organisms from which they were extracted. We find that the folding free energy at the temperature of maximal stability is significantly more favorable in thermophiles than in mesophiles, whereas the maximal stability temperature itself is similar between these two classes. Furthermore, we extend the thermodynamic analysis to model the entire proteome. The results explain the high optimal growth temperature in thermophilic organisms and are in excellent quantitative agreement with full thermal growth rate data obtained in a dozen thermophilic and mesophilic organisms.