An electrostatic basis for the stability of thermophilic proteins
An electrostatic basis for the stability of thermophilic proteins
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DOI：
10.1002/prot.20190
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发表时间：
2004-10-01
影响因子：
2.9
通讯作者：
Brooks, CL
中科院分区：
文献类型：
--
作者：
Dominy, BN;Minoux, H;Brooks, CL
有两个因素对嗜热蛋白相对于其嗜温同系物的稳定性、折叠中带电残基的静电相互作用、折叠蛋白的状态和介电响应做出了关键贡献。对于“嗜热系列”中的蛋白质，介电响应全局调节其成员的热稳定性，计算出的蛋白质介电常数从嗜温菌到超嗜热菌增加。这种变异性是由于蛋白质表面带电残基分布的差异造成的，与结构和遗传观察一致。此外，静电相互作用对折叠状态稳定性的贡献对于嗜热蛋白质比对其嗜温同系物更有利。由此得出的结论是，静电相互作用在决定蛋白质在高温下的稳定性方面发挥着重要作用。静电相互作用和介电响应之间的相互作用也为嗜热蛋白质在冷变性方面增强的稳定性提供了进一步的合理化。总而言之，带电残基的分布及其波动已被证明是在整个生物学相关温度范围内调节蛋白质稳定性的因素。 (C) 2004 Wiley-Liss, Inc.
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 foe 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. (C) 2004 Wiley-Liss, Inc.