Baldwin R L
Department of Biochemistry, Beckman Center, Stanford University Medical Center, California 94305-5307 USA.
Biophys J. 1996 Oct;71(4):2056-63. doi: 10.1016/S0006-3495(96)79404-3.
Model compound studies in the literature show how Hofmeister ion interactions affect protein stability. Although model compound results are typically obtained as salting-out constants, they can be used to find out how the interactions affect protein stability. The null point in the Hofmeister series, which divides protein denaturants from stabilizers, arises from opposite interactions with different classes of groups: Hofmeister ions salt out nonpolar groups and salt in the peptide group. Theories of how Hofmeister ion interactions work need to begin by explaining the mechanisms of these two classes of interactions. Salting-out nonpolar groups has been explained by the cavity model, but its use is controversial. When applied to model compound data, the cavity model 1) uses surface tension increments to predict the observed values of the salting-out constants, within a factor of 3, and 2) predicts that the salting-out constant should increase with the number of carbon atoms in the aliphatic side chain of an amino acid, as observed. The mechanism of interaction between Hofmeister ions and the peptide group is not well understood, and it is controversial whether this interaction is ion-specific, or whether it is nonspecific and the apparent specificity resides in interactions with nearby nonpolar groups. A nonspecific salting-in interaction is known to occur between simple ions and dipolar molecules; it depends on ionic strength, not on position in the Hofmeister series. A theory by Kirkwood predicts the strength of this interaction and indicates that it depends on the first power of the ionic strength. Ions interact with proteins in various ways besides the Hofmeister ion interactions discussed here, especially by charge interactions. Much of what is known about these interactions comes from studies by Serge Timasheff and his co-workers. A general model, suitable for analyzing diverse ion-protein interactions, is provided by the two-domain model of Record and co-workers.
文献中的模型化合物研究表明了霍夫迈斯特离子相互作用如何影响蛋白质稳定性。尽管模型化合物的结果通常以盐析常数的形式获得，但它们可用于探究这些相互作用如何影响蛋白质稳定性。霍夫迈斯特序列中的零点将蛋白质变性剂与稳定剂区分开来，这源于与不同类型基团的相反相互作用：霍夫迈斯特离子使非极性基团盐析，而使肽基团盐溶。关于霍夫迈斯特离子相互作用如何起作用的理论需要首先解释这两类相互作用的机制。非极性基团的盐析已由空腔模型解释，但该模型的应用存在争议。当应用于模型化合物数据时，空腔模型：1）使用表面张力增量来预测盐析常数的观测值，误差在3倍以内；2）预测盐析常数应随氨基酸脂肪族侧链中碳原子数的增加而增加，这与观测结果一致。霍夫迈斯特离子与肽基团之间的相互作用机制尚未完全理解，这种相互作用是否具有离子特异性，或者它是否是非特异性的，而表面上的特异性存在于与附近非极性基团的相互作用中，这一点存在争议。已知简单离子与偶极分子之间会发生非特异性盐溶相互作用；它取决于离子强度，而不取决于在霍夫迈斯特序列中的位置。柯克伍德的一个理论预测了这种相互作用的强度，并表明它取决于离子强度的一次幂。除了这里讨论的霍夫迈斯特离子相互作用外，离子还以各种方式与蛋白质相互作用，尤其是通过电荷相互作用。关于这些相互作用的许多已知信息来自塞尔日·蒂马舍夫及其同事的研究。里德及其同事的双结构域模型提供了一个适用于分析各种离子 - 蛋白质相互作用的通用模型。
