Department of Physics and Astronomy, University of Denver, Denver, Colorado, USA.
Biophys J. 2010 Dec 15;99(12):3996-4002. doi: 10.1016/j.bpj.2010.10.036.
Biological cells are extremely sensitive to temperature. What is the mechanism? We compute the thermal stabilities of the whole proteomes of Escherichia coli, yeast, and Caenorhabditis elegans using an analytical model and an extensive database of stabilities of individual proteins. Our results support the hypothesis that a cell's thermal sensitivities arise from the collective instability of its proteins. This model shows a denaturation catastrophe at temperatures of 49-55°C, roughly the thermal death point of mesophiles. Cells live on the edge of a proteostasis catastrophe. According to the model, it is not that the average protein is problematic; it is the tail of the distribution. About 650 of E. coli's 4300 proteins are less than 4 kcal mol(-1) stable to denaturation. And upshifting by only 4° from 37° to 41°C is estimated to destabilize an average protein by nearly 20%. This model also treats effects of denaturants, osmolytes, and other physical stressors. In addition, it predicts the dependence of cellular growth rates on temperature. This approach may be useful for studying physical forces in biological evolution and the role of climate change on biology.
生物细胞对温度极其敏感。其机制是什么？我们使用分析模型和大量单个蛋白质稳定性数据库，计算了大肠杆菌、酵母和秀丽隐杆线虫的整个蛋白质组的热稳定性。我们的结果支持这样一种假设，即细胞的热敏感性源于其蛋白质的集体不稳定性。该模型在 49-55°C 的温度下显示出变性崩溃，大致为中温生物的热致死点。细胞生活在蛋白质稳定的崩溃边缘。根据该模型，问题不在于平均蛋白质，而是分布的尾部。大肠杆菌的 4300 种蛋白质中，约有 650 种的变性稳定性低于 4 千卡摩尔(-1)。从 37°C 升高到 41°C 仅 4°C，估计会使平均蛋白质的稳定性降低近 20%。该模型还可以处理变性剂、渗透剂和其他物理胁迫剂的影响。此外，它还预测了细胞生长速率对温度的依赖性。这种方法可能有助于研究生物进化中的物理力以及气候变化对生物学的影响。
