England Jeremy L, Haran Gilad
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.
Annu Rev Phys Chem. 2011;62:257-77. doi: 10.1146/annurev-physchem-032210-103531.
Protein stability often is studied in vitro through the use of urea and guanidinium chloride, chemical cosolvents that disrupt protein native structure. Much controversy still surrounds the underlying mechanism by which these molecules denature proteins. Here we review current thinking on various aspects of chemical denaturation. We begin by discussing classic models of protein folding and how the effects of denaturants may fit into this picture through their modulation of the collapse, or coil-globule transition, which typically precedes folding. Subsequently, we examine recent molecular dynamics simulations that have shed new light on the possible microscopic origins of the solvation effects brought on by denaturants. It seems likely that both denaturants operate by facilitating solvation of hydrophobic regions of proteins. Finally, we present recent single-molecule fluorescence studies of denatured proteins, the analysis of which corroborates the role of denaturants in shifting the equilibrium of the coil-globule transition.
蛋白质稳定性通常在体外通过使用尿素和氯化胍来研究，这两种化学共溶剂会破坏蛋白质的天然结构。关于这些分子使蛋白质变性的潜在机制仍然存在很多争议。在此，我们综述了当前对化学变性各个方面的看法。我们首先讨论蛋白质折叠的经典模型，以及变性剂的作用如何通过调节折叠前通常发生的塌陷或卷曲-球状转变而融入这一图景。随后，我们研究了最近的分子动力学模拟，这些模拟为变性剂带来的溶剂化效应的可能微观起源提供了新的线索。这两种变性剂似乎都是通过促进蛋白质疏水区域的溶剂化来发挥作用的。最后，我们展示了最近对变性蛋白质的单分子荧光研究，对其分析证实了变性剂在改变卷曲-球状转变平衡中的作用。
