Studying salt effects on protein stability using ribonuclease t1 as a model system
Studying salt effects on protein stability using ribonuclease t1 as a model system
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DOI：
10.1016/j.bpc.2011.11.004
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发表时间：
2012-02-01
影响因子：
3.8
通讯作者：
Khajehpour, Mazdak
中科院分区：
文献类型：
--
作者：
Beauchamp, David L.;Khajehpour, Mazdak
盐离子以多种方式影响蛋白质的稳定性。一般来说，这些效应要么从电荷溶剂化/电荷屏蔽的角度解释，要么被认为是离子与特定蛋白质特异性相互作用的结果。最近的理论工作表明，盐对蛋白质的影响的主要贡献是通过位于蛋白质表面附近的盐离子和位于低介电蛋白质腔中的诱导点像电荷的相互作用。这些相互作用形成“盐析”相互作用的基础。盐离子在低介电蛋白质介质中诱导相同符号的图像电荷。感应电荷和它的镜像电荷之间的相互作用是排斥的，因此是不稳定的。然而，具有小得多的表面积的折叠蛋白质将比未折叠状态更不稳定。因此，折叠状态将相对于展开状态稳定。这项工作分析了模型酶核糖核酸酶t1中的盐效应，并证明了盐离子和它们诱导的点电荷之间的相互作用对所观察到的盐诱导的蛋白质稳定性增加做出了重大贡献。这项工作还表明，在弱结合离子的情况下（离子的结合常数是在50 M-1和更少的顺序），盐析效应仍应考虑，以提供一个更现实的解释离子结合。因此，这些结果应考虑盐的影响时，用于分析蛋白质结构的静电贡献，或用于研究与嗜盐生物相关的蛋白质的热力学。(C)2011 Elsevier B. V.保留所有权利。
Salt ions affect protein stability in a variety of ways. In general, these effects have either been interpreted from a charge solvation/charge screening standpoint or they have been considered to be the result of ion-specific interactions with a particular protein. Recent theoretical work suggests that a major contribution to salt effects on proteins is through the interaction of salt ions that are located near the protein surface and their induced point image charges that are located in the low-dielectric protein cavity. These interactions form the basis of "salting-out" interactions. Salt ions induce an image charge of the same sign in the low dielectric protein medium. The interaction between the induced charge and its mirror charge is repulsive and consequently thermodynamically destabilizing. However, a folded protein that has a much smaller surface area will be less destabilized than the unfolded state. Consequently, the folded state will be stabilized relative to the unfolded state. This work analyzes salt effects in the model enzyme ribonuclease t1, and demonstrates that interactions between salt ions and their induced point charges provide a major contribution to the observed salt-induced increase in protein stability. This work also demonstrates that in the case of weakly-binding ions (ions with binding constants that are in the order of 50 M-1 and less), salting-out effects should still be considered in order to provide a more realistic interpretation of ion binding. These results should therefore be considered when salt effects are used to analyze electrostatic contributions to protein structure or are used to study the thermodynamics of proteins associated with halophillic organisms. (C) 2011 Elsevier B.V. All rights reserved.