美国斯坦福大学医学院冯亮和哈佛大学医学院廖茂富研究组，共同发现了CCC共转运体NKCC1的结构与机理。该论文于2019年8月22日发表在《自然》上。

该研究确定了Na-K-Cl协同转运蛋白NKCC1的冷冻电镜结构，NKCC1是斑马鱼中的一个被广泛研究的CCC家族成员。该结构定义了该蛋白质家族的架构，并揭示了在细胞溶质和跨膜结构域中如何精确定位以便进行交流。结构分析和功能特性以及计算研究结果揭示了离子转定位的途径、离子结合位点以及与运输活性有关的关键残基。研究结果为离子选择性，偶联，转定位和建立一个了解CCC生理功能的框架以及解释疾病相关的突变提供了新的视角。

据介绍，CCC介导膜上的氯离子、钾和/或钠的电中性转运。它们在调节细胞体积，控制上皮细胞的离子吸收和分泌以及维持细胞内氯化物稳态方面具有关键作用。这些转运蛋白是一些最常用处方药的主要靶点。

附：英文原文

Title: Structure and mechanism of the cation–chloride cotransporter NKCC1

Author: Thomas A. Chew, Benjamin J. Orlando, Jinru Zhang, Naomi R. Latorraca, Amy Wang, Scott A. Hollingsworth, Dong-Hua Chen, Ron O. Dror, Maofu Liao, Liang Feng

Issue&Volume: Volume 572 Issue 7770

Abstract: Cationchloride cotransporters (CCCs) mediate the electroneutral transport of chloride, potassium and/or sodium across the membrane. They have critical roles in regulating cell volume, controlling ion absorption and secretion across epithelia, and maintaining intracellular chloride homeostasis. These transporters are primary targets for some of the most commonly prescribed drugs. Here we determined the cryo-electron microscopy structure of the NaKCl cotransporter NKCC1, an extensively studied member of the CCC family, from Danio rerio. The structure defines the architecture of this protein family and reveals how cytosolic and transmembrane domains are strategically positioned for communication. Structural analyses, functional characterizations and computational studies reveal the ion-translocation pathway, ion-binding sites and key residues for transport activity. These results provide insights into ion selectivity, coupling and translocation, and establish a framework for understanding the physiological functions of CCCs and interpreting disease-related mutations.

DOI: 10.1038/s41586-019-1438-2

Source:https://www.nature.com/articles/s41586-019-1438-2