Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.
State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
Commun Biol. 2021 Feb 17;4(1):226. doi: 10.1038/s42003-021-01750-w.
NKCC and KCC transporters mediate coupled transport of Na+K+Cl and K+Cl across the plasma membrane, thus regulating cell Cl concentration and cell volume and playing critical roles in transepithelial salt and water transport and in neuronal excitability. The function of these transporters has been intensively studied, but a mechanistic understanding has awaited structural studies of the transporters. Here, we present the cryo-electron microscopy (cryo-EM) structures of the two neuronal cation-chloride cotransporters human NKCC1 (SLC12A2) and mouse KCC2 (SLC12A5), along with computational analysis and functional characterization. These structures highlight essential residues in ion transport and allow us to propose mechanisms by which phosphorylation regulates transport activity.
NKCC 和 KCC 转运体介导 Na+K+Cl 和 K+Cl 在质膜上的偶联转运，从而调节细胞 Cl 浓度和细胞体积，并在跨上皮盐和水转运以及神经元兴奋性中发挥关键作用。这些转运体的功能已经得到了深入研究，但对其结构的研究一直等待对转运体的结构研究。在这里，我们展示了两种神经元阳离子-氯离子共转运体人 NKCC1（SLC12A2）和小鼠 KCC2（SLC12A5）的冷冻电子显微镜（cryo-EM）结构，以及计算分析和功能表征。这些结构突出了离子转运中的关键残基，并使我们能够提出磷酸化调节转运活性的机制。
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