Water penetration in the low and high pressure native states of ubiquitin
Water penetration in the low and high pressure native states of ubiquitin
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DOI：
10.1002/prot.21562
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发表时间：
2008-03-01
影响因子：
2.9
通讯作者：
Garcia, Angel E.
中科院分区：
文献类型：
--
作者：
Day, Ryan;Garcia, Angel E.
对甲烷分子在水中的溶剂化作用的理论研究表明，相对于直接接触，增加压力的效果是稳定溶剂分离接触。这表明，高压使渗透到蛋白质核心的沃茨稳定，表明了蛋白质高压变性的机制。我们通过研究水在低压和高压下渗透到泛素的天然状态来测试折叠蛋白质的理论，使用分子动力学。在折叠状态下的泛素采样的构象的合奏已被确定在两个压力低于蛋白质的变性压力，30大气压和3000大气压的NMR。我们发现，1-5更多的沃茨渗透的高压构象比低压构象。系统的低体积配置在高压下是有利的，但是系统的不同部件可能经历其比容的增加或减少。我们发现，渗透沃茨有一个较高的体积，每水比散装沃茨，但每蛋白质残留物的体积可能会降低溶剂化。此外，我们发现，渗透的蛋白质在高压下由水驱动的差异的压力依赖性的概率在蛋白质中的空腔开口和压力依赖性的概率在散装溶剂中的空腔开口。与空腔打开和关闭相关的体积变化表明，每次渗透的水使系统的体积减少约12 mL/mol。泛素从低压到高压天然状态的实验体积变化为24 mL/mol。我们的研究结果表明，这种体积变化可以解释由两个水分子的蛋白质的渗透。
Theoretical studies on the solvation of methane molecules in water have shown that the effect of increased pressure is to stabilize solvent separated contacts relative to direct contacts. This suggests that high pressure stabilizes waters that have penetrated into a protein's core, indicating a mechanism for the high pressure denaturation of proteins. We test this theory on a folded protein by studying the penetration of water into the native state of ubiquitin at low and high pressures, using molecular dynamics. An ensemble of conformations sampled in the folded state of ubiquitin has been determined by NMR at two pressures below the protein's denaturation pressure, 30 atm and 3000 atm. We find that 1-5 more waters penetrate the high pressure conformations than the low pressure conformations. Low volume configurations of the system are favored at high pressures, but different components of the system may experience increases or decreases in their specific volumes. We find that penetrating waters have a higher volume per water than bulk waters, but that the volume per protein residue may be lowered by solvation. Furthermore, we find that penetration of the protein by water at high pressures is driven by the difference in the pressure dependence of the probability of cavity opening in the protein and pressure dependence of the probability of cavity opening in the bulk solvent. The volume changes associated with cavity opening and closing indicate that each penetrating water reduces the volume of the system by about 12 mL/mol. The experimental volume change going from the low pressure to the high pressure native state of ubiquitin is 24 mL/mol. Our results indicate that this volume change can be explained by penetration of the protein by two water molecules.