Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
J Chem Phys. 2012 Oct 14;137(14):145101. doi: 10.1063/1.4757419.
To investigate how solvent (water) and cosolvent (osmolyte) affect protein structure in various osmolyte solutions, in the present study we used GB1p peptide as the model protein to study its folding process in 2,2,2-trifluoroethanol (TFE)∕water and denaturation process in GdmSCN∕water solutions, respectively. It was observed that TFE moderately enhances the structure stability of native β-hairpin, consistent with the previous experimental observation that the hairpin conformation population of several polypeptides is increased in TFE∕water solution compared to in pure water. More interestingly, the formation of β-hairpin is significantly accelerated in TFE∕water solution. The accelerated folding of β-hairpin consists of following sequential events: the accumulation of TFE on protein surface → less water surrounding carbonyl group (easier dehydration of CO) → the formation of CO-NH backbone hydrogen bond. In contrary, the denaturation of hairpin structure of GB1p peptide in GdmSCN∕water solution is induced by the accumulation of Gdm(+) on protein surface and the hydrogen bonding from water as well as Gdm(+). Therefore, this study shows the importance of water in TFE-induced formation and Gdm(+)-induced denaturation of β-hairpin structure.
为了研究溶剂（水）和共溶剂（渗透剂）在各种渗透剂溶液中如何影响蛋白质结构，本研究以 GB1p 肽作为模型蛋白，分别研究其在 2,2,2-三氟乙醇（TFE）/水和在 GdmSCN/水中的变性过程中的折叠过程。结果表明，TFE 适度增强了天然 β-发夹结构的稳定性，与之前的实验观察结果一致，即在 TFE/水溶液中，与纯水中相比，几种多肽的发夹构象群体增加。更有趣的是，β-发夹在 TFE/水溶液中的形成明显加快。β-发夹的加速折叠包括以下顺序事件：TFE 在蛋白质表面的积累→羰基周围的水减少（更容易脱去 CO）→CO-NH 骨架氢键的形成。相反，GB1p 肽在 GdmSCN/水溶液中的发夹结构的变性是由蛋白质表面上 Gdm(+)的积累以及来自水和 Gdm(+)的氢键引起的。因此，本研究表明了水在 TFE 诱导的β-发夹形成和 Gdm(+)诱导的β-发夹变性中的重要性。
