Pressure effects on structures formed by entropically driven self-assembly: illustration for denaturation of proteins.
Pressure effects on structures formed by entropically driven self-assembly: illustration for denaturation of proteins.
复制标题
压力对由熵驱动的自组装形成的结构的影响：蛋白质变性的图示。
DOI：
10.1103/physreve.79.011912
复制
发表时间：
2009
期刊：
影响因子：
--
通讯作者：
M. Kinoshita
中科院分区：
文献类型：
--
作者：
Takashi Yoshidome;Y. Harano;M. Kinoshita
我们提出了一个一般框架的压力对所形成的结构的溶质分子浸没在溶剂中的自组装的影响。将积分方程理论与形态学方法相结合，用于刚体模型系统。我们的观点是，蛋白质折叠和蛋白质的有序缔合是由溶剂熵驱动的：在低压下，几乎使溶剂颗粒产生的排斥体积（EV）最小化的结构是稳定的。这种结构在高压下似乎更加稳定。然而，实验上已知蛋白质的天然结构是未折叠的，并且通过施加高压使有序聚集体如淀粉样原纤维和肌动蛋白丝解离。这个最初令人困惑的结果也可以用溶剂熵来解释。基本机制的线索是这样一种现象，即当大的硬球溶质浸入形成溶剂的小的硬球中时，小的硬球在溶质附近富集，并且这种富集随着压力的增加而变得更大。我们认为，“吸引力”之间的溶质表面和溶剂颗粒的熵提供，并增加压力的吸引力变得更高。由于这种效应，在高压下，具有最大可能的溶剂可及表面积以及足够小的EV的结构在溶剂熵方面变得更稳定。为了说明这一概念，我们对三种不同蛋白质的压力变性进行了分析。它表明，只有具有上述特征的结构表现出有趣的行为。随着压力的增加，它们首先相对于天然结构变得更加不稳定，但是超过阈值压力，相对不稳定性开始降低，并且它们最终变得比天然结构更稳定。
We propose a general framework of pressure effects on the structures formed by the self-assembly of solute molecules immersed in solvent. The integral equation theory combined with the morphometric approach is employed for a hard-body model system. Our picture is that protein folding and ordered association of proteins are driven by the solvent entropy: At low pressures, the structures almost minimizing the excluded volume (EV) generated for solvent particles are stabilized. Such structures appear to be even more stabilized at high pressures. However, it is experimentally known that the native structure of a protein is unfolded, and ordered aggregates such as amyloid fibrils and actin filaments are dissociated by applying high pressures. This initially puzzling result can also be elucidated in terms of the solvent entropy. A clue to the basic mechanism is in the phenomenon that, when a large hard-sphere solute is immersed in small hard spheres forming the solvent, the small hard spheres are enriched near the solute and this enrichment becomes greater as the pressure increases. We argue that "attraction" is entropically provided between the solute surface and solvent particles, and the attraction becomes higher with rising pressure. Due to this effect, at high pressures, the structures possessing the largest possible solvent-accessible surface area together with sufficiently small EV become more stable in terms of the solvent entropy. To illustrate this concept, we perform an analysis of pressure denaturation of three different proteins. It is shown that only the structures that have the characteristics described above exhibit interesting behavior. They first become more destabilized relative to the native structure as the pressure increases, but beyond a threshold pressure the relative instability begins to decrease and they eventually become more stable than the native structure.