Structural basis for molecular mechanisms of substrate recognition and transport regulation by membrane transporters

膜转运蛋白通过严格调节金属离子、糖、代谢物和药物等的进出口来维持细胞内环境。为了阐明(A)转运体如何驱动其运输，(B)转运体如何独家选择其特定底物，以及(C)转运体如何在原子分辨率上调节其运输活动，我们进行了(1)x射线晶体学结构测定，(2)MD模拟动态特性分析和(3)体内和体外互补实验，重点研究了镁、铁和重金属离子转运体，光门控阳离子通道，蛋白质转运蛋白，肽转运蛋白和多药转运蛋白。特别是，我们通过比较和整合不同类型目标溶质特异性转运蛋白的功能机制，揭示了膜运输的基本分子机制。

Membrane transporters maintain the intracellular circumstances by strictly regulating the import and export of metal ions, sugars, metabolites and drugs etc. To elucidate (A) how the transporters drive their transport, (B) how the transporters exclusively select their specific substrates and (C) how the transporters regulate their transporting activities at at an atomic resolution, we performed (1) structure determination by X-ray crystallography, (2) dynamic property analysis by MD simulation and (3) in vivo and in vitro complementary experiments, focusing on ion transporters of magnesium, iron and heavy metals, light-gated cation channels, protein transporters, peptide transporter and multidrug transporters. Especially, we uncovered the essential molecular mechanism of membrane transport by comparing and integrating the functional mechanisms of transporters specific for various kinds of target solutes.