Ji Wanying, Shi Donghong, Shi Sai, Yang Xiao, Chen Yafei, An Hailong, Pang Chunli
Institute of Biophysics, School of Science, Hebei University of Technology, Tianjin 300401, China.
Institute of Biophysics, School of Science, Hebei University of Technology, Tianjin 300401, China | State Key Laboratory of Reliability and Intelligence of Electrical Equipment, Hebei University of Technology, Tianjin 300401, China.
Protein Pept Lett. 2021;28(12):1338-1348. doi: 10.2174/0929866528666211105112131.
TMEM16A mediates the calcium-activated transmembrane flow of chloride ions and a variety of physiological functions. The binding of cytoplasmic calcium ions of TMEM16A and the consequent conformational changes of it are the key issues to explore the structure-function relationship. In recent years, researchers have explored this issue through electrophysiological experiments, structure resolving, molecular dynamic simulation, and other methods. The structures of TMEM16 family members determined by cryo-Electron microscopy (cryo-EM) and X-ray crystallization provide the primary basis for the investigation of the molecular mechanism of TMEM16A. However, the binding and activation mechanism of calcium ions in TMEM16A are still unclear and controversial. This mini-review discusses four Ca sensing sites of TMEM16A and analyzes activation properties of TMEM16A by them, which will help understand the structure-function relationship of TMEM16A and throw light on the molecular design targeting the TMEM16A channel.
TMEM16A介导氯离子的钙激活跨膜流动及多种生理功能。TMEM16A的胞质钙离子结合及其随之发生的构象变化是探索其结构-功能关系的关键问题。近年来，研究人员通过电生理实验、结构解析、分子动力学模拟等方法对这一问题进行了探索。通过冷冻电子显微镜（cryo-EM）和X射线晶体学确定的TMEM16家族成员结构为研究TMEM16A的分子机制提供了主要依据。然而，TMEM16A中钙离子的结合和激活机制仍不明确且存在争议。本综述讨论了TMEM16A的四个钙传感位点，并分析了它们对TMEM16A的激活特性，这将有助于理解TMEM16A的结构-功能关系，并为针对TMEM16A通道的分子设计提供思路。
