Dynamic control of protein structure by cation-π interaction

我们利用圆二色谱（CD）、荧光和紫外共振拉曼光谱研究了正电荷与π电子之间的相互作用，即阳离子-π相互作用对蛋白质结构形成和动力学的影响。研究的肽和蛋白质是神经介肽B、神经介肽C和流感B病毒BM 2蛋白的跨膜区（BM 2-TMP）。发现His^+和Trp之间的阳离子-π相互作用不能控制神经介肽B和C的二级结构，这表明这种阳离子-π相互作用对蛋白质结构稳定性没有太大贡献。然而，类似的阳离子-π相互作用在脂质双层中门控由BM 2-TMP形成的质子通道中起重要作用，表明阳离子-π相互作用可以通过修饰功能重要区域附近的局部结构来控制蛋白质的功能。此外，Cu^<2+>与Trp之间的阳离子-π相互作用不仅使Trp吲哚环的紫外吸收峰发生位移和强度变化，而且在圆二色光谱中产生负信号。CD负信号有望作为蛋白质中Cu^<2+>与Trp之间阳离子-π相互作用的新标记。如在由BM 2-TMP形成的质子通道的情况下所示，阳离子-π相互作用可以在与其功能相关的蛋白质的结构动力学中发挥重要作用。虽然目前提出的关于阳离子-α相互作用在蛋白质功能中的作用需要在许多其他蛋白质中进一步测试，但本研究为此类未来研究提供了基础。

We have studied the effects of interaction between a positive charge and π electrons, i.e. cation-π interaction, on the structural formation and dynamics of proteins by circular dichroism (CD), fluorescence, and UV resonance Raman spectroscopy. The peptides and proteins studied are neuromedin B, neuromedin C, and the transmembrane region of influenza B virus BM2 protein (BM2-TMP). The cation-π interaction between His^+ and Trp was found to be unable to control the secondary structures of neuromedin B and C, suggesting that such cation-π interactions do not so much contribute to protein structural stability. However, analogous cation-π interactions play an important role in gating a proton channel formed by BM2-TMP in lipid bilayers, demonstrating that cation-π interactions can control the functioning of a protein by modifying its local structure near functionally important regions. In addition, cation-π interaction between Cu^<2+> and Trp was found to cause not only a shift and intensity change of UV absorption of the Trp indole ring but also to generate a negative signal in CD spectra. The negative CD signal is expected to serve as a new marker of cation-π interaction between Cu^<2+> and Trp in proteins. As shown in the case of the proton channel formed by BM2-TMP, cation-π interactions could play important roles in structural dynamics of proteins associated with their functioning. Although the present proposal about the role of cation-a interaction in protein functioning need to be further tested in many other proteins, the present study has provided the basis of such future studies.