Dominy Brian N, Minoux Hervé, Brooks Charles L
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts, USA.
Proteins. 2004 Oct 1;57(1):128-41. doi: 10.1002/prot.20190.
Two factors provide key contributions to the stability of thermophilic proteins relative to their mesophilic homologues: electrostatic interactions of charged residues in the folded state and the dielectric response of the folded protein. The dielectric response for proteins in a "thermophilic series" globally modulates the thermal stability of its members, with the calculated dielectric constant for the protein increasing from mesophiles to hyperthermophiles. This variability results from differences in the distribution of charged residues on the surface of the protein, in agreement with structural and genetic observations. Furthermore, the contribution of electrostatic interactions to the stability of the folded state is more favorable for thermophilic proteins than for their mesophilic homologues. This leads to the conclusion that electrostatic interactions play an important role in determining the stability of proteins at high temperatures. The interplay between electrostatic interactions and dielectric response also provides further rationalization for the enhanced stability of thermophilic proteins with respect to cold-denaturation. Taken together, the distribution of charged residues and their fluctuations have been shown to be factors in modulating protein stability over the entire range of biologically relevant temperatures.
与中温同源蛋白相比，有两个因素对嗜热蛋白的稳定性起着关键作用：折叠状态下带电残基的静电相互作用以及折叠蛋白的介电响应。“嗜热蛋白系列”中蛋白质的介电响应全局调节其成员的热稳定性，随着从嗜温菌到超嗜热菌，计算出的蛋白质介电常数增加。这种变化源于蛋白质表面带电残基分布的差异，这与结构和遗传学观察结果一致。此外，静电相互作用对折叠状态稳定性的贡献对嗜热蛋白比对其中温同源蛋白更有利。这得出结论，静电相互作用在决定蛋白质在高温下的稳定性中起重要作用。静电相互作用和介电响应之间的相互作用也为嗜热蛋白相对于冷变性增强的稳定性提供了进一步的合理解释。综上所述，带电残基的分布及其波动已被证明是在生物相关温度的整个范围内调节蛋白质稳定性的因素。
