The effects of ionic strength on protein stability: The cold shock protein family
The effects of ionic strength on protein stability: The cold shock protein family
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DOI：
10.1016/s0022-2836(02)00259-0
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发表时间：
2002-05-31
影响因子：
5.6
通讯作者：
Brooks, CL
中科院分区：
文献类型：
--
作者：
Dominy, BN;Perl, D;Brooks, CL
连续统静电模型被用来详细研究蛋白质的稳定和不稳定的机制，由于盐接近生理浓度。三个野生型冷休克蛋白取自嗜温，嗜热，超嗜热细菌使用这些方法进行了研究。通过与这些蛋白质收集的实验数据进行比较，该模型得到验证。此外，一些单点突变体和三个设计的序列进行了检查。本研究结果表明，在冷休克蛋白家族中，蛋白质对盐的稳定性的敏感性与热稳定性相关。计算表明，盐的存在使嗜温菌稳定，而使嗜热菌和超嗜热菌不稳定。在残基水平上对盐影响的分解允许鉴定有助于观察到的盐依赖性稳定性的蛋白质序列区域。该模型用于合理化各种点突变对盐敏感性的影响。最后，它表明，设计的冷休克蛋白变体表现出类似于天然的嗜热和超嗜热蛋白的静电特性。(C)2002爱思唯尔科技有限公司。保留所有权利。
Continuum electrostatic models are used to examine in detail the mechanism of protein stabilization and destabilization due to salt near physiological concentrations. Three wild-type cold shock proteins taken from mesophilic, thermophilic, and hyperthermophilic bacteria are studied using these methods. The model is validated by comparison with experimental data collected for these proteins. In addition, a number of single point mutants and three designed sequences are examined. The results from this study demonstrate that the sensitivity of protein stability toward salt is correlated with thermostability in the cold shock protein family. The calculations indicate that the mesophile is stabilized by the presence of salt while the thermophile and hyperthermophile are destabilized. A decomposition of the salt influence at a residue level permits identification of regions of the protein sequences that contribute toward the observed salt-dependent stability. This model is used to rationalize the effect of various point mutations with regard to sensitivity toward salt. Finally, it is demonstrated that designed cold shock protein variants exhibit electrostatic properties similar to the natural thermophilic and hyperthermophilic proteins. (C) 2002 Elsevier Science Ltd. All rights reserved.