Two different regimes in alcohol-induced coil?helix transition: effects of 2,2,2-trifluoroethanol on proteins being either independent of or enhanced by solvent structural fluctuations
Two different regimes in alcohol-induced coil?helix transition: effects of 2,2,2-trifluoroethanol on proteins being either independent of or enhanced by solvent structural fluctuations
复制标题
酒精诱导的螺旋转变的两种不同机制：2,2,2-三氟乙醇对蛋白质的影响独立于溶剂结构波动或通过溶剂结构波动增强
DOI：
10.1039/d0cp05103a
复制
发表时间：
2021
影响因子：
3.3
通讯作者：
Morita Takeshi
中科院分区：
文献类型：
--
作者：
Ohgi Hiroyo;Imamura Hiroshi;Sumi Tomonari;Nishikawa Keiko;Koga Yoshikata;Westh Peter;Morita Takeshi
已知组成分子在混合溶剂中的不均匀分布对溶质产生显著影响，例如，生物分子在醇-水混合物中的构象变化。我们研究了2，2，2-三氟乙醇（TFE）对蛋白质/肽在水和TFE的混合物中使用蜂毒素作为模型蛋白质的一般影响。波动和Kirkwood-Buff积分（KBIs）在TFE-H2O混合物，定量描述的不均匀性，测定了小角X射线散射调查，并与其他醇的水溶液中的那些进行了比较。混合物的浓度波动排列为甲醇<乙醇> TFE <叔丁醇< 1-丙醇，表明TFE-H2O混合物中分子分布的不均匀性出乎意料地与一元醇系列中的那些相当。在TFE分子之间KBI的浓度依赖性的基础上，发现TFE分子之间的强吸引力对于诱导螺旋构象并不一定重要，这与先前提出的机制不一致。为了解决这个问题，通过结合KBI和螺旋内容的实验光谱研究报告，我们定量评估的变化，在优先结合参数的TFE蜂毒肽归因于线圈-螺旋过渡。因此，我们发现了两种不同的制度对TFE诱导的螺旋形成。在稀浓度区的TFE低于1002 M，其中的TFE分子之间不聚集，过量的优先结合的TFE的螺旋发生由于它们之间的直接相互作用，即独立的溶剂波动。在高于1002 M的较高浓度区域，除了前者的效果，过量的优先结合显着增强的溶剂波动。该方案应被视为TFE对蛋白质/肽的一般共溶剂效应。
Inhomogeneous distribution of constituent molecules in a mixed solvent has been known to give remarkable effects on the solute, e.g., conformational changes of biomolecules in an alcohol–water mixture. We investigated the general effects of 2,2,2-trifluoroethanol (TFE) on proteins/peptides in a mixture of water and TFE using melittin as a model protein. Fluctuations and Kirkwood–Buff integrals (KBIs) in the TFE–H2O mixture, quantitative descriptions of inhomogeneity, were determined by small-angle X-ray scattering investigation and compared with those in the aqueous solutions of other alcohols. The concentration fluctuation for the mixtures ranks as methanol < ethanol ≪ TFE < tert-butanol < 1-propanol, indicating that the inhomogeneity of molecular distribution in the TFE–H2O mixture is unexpectedly comparable to those in the series of mono-ols. On the basis of the concentration dependence of KBIs between the TFE molecules, it was found that a strong attraction between the TFE molecules is not necessarily important to induce helix conformation, which is inconsistent with the previously proposed mechanism. To address this issue, by combining the KBIs and the helix contents reported by the experimental spectroscopic studies, we quantitatively evaluated the change in the preferential binding parameter of TFE to melittin attributed to the coil–helix transition. As a result, we found two different regimes on TFE-induced helix formation. In the dilute concentration region of TFE below ∼2 M, where the TFE molecules are not aggregated among themselves, the excess preferential binding of TFE to the helix occurs due to the direct interaction between them, namely independent of the solvent fluctuation. In the higher concentration region above ∼2 M, in addition to the former effect, the excess preferential binding is significantly enhanced by the solvent fluctuation. This scheme should be held as general cosolvent effects of TFE on proteins/peptides.