Volume 9 Issue 7
Jul.  2018
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Jie Yu, Bing Zhang, Yixiao Zhang, Cong-qiao Xu, Wei Zhuo, Jingpeng Ge, Jun Li, Ning Gao, Yang Li, Maojun Yang. A binding-block ion selective mechanism revealed by a Na/K selective channel[J]. Protein&Cell, 2018, 9(7): 629-639. doi: 10.1007/s13238-017-0465-8
Citation: Jie Yu, Bing Zhang, Yixiao Zhang, Cong-qiao Xu, Wei Zhuo, Jingpeng Ge, Jun Li, Ning Gao, Yang Li, Maojun Yang. A binding-block ion selective mechanism revealed by a Na/K selective channel[J]. Protein&Cell, 2018, 9(7): 629-639. doi: 10.1007/s13238-017-0465-8

A binding-block ion selective mechanism revealed by a Na/K selective channel

doi: 10.1007/s13238-017-0465-8

We thank the Tsinghua University Branch of China National Center for Protein Sciences (Beijing) for providing the facility support. The computation was completed on the "Explorer 100" cluster system of Tsinghua National Laboratory for Information Science and Technology. We also thank Samantha Miller (University of Aberdeen, UK) for helpful discussion. This work was supported by funds from the Ministry of Science and Technology (2016YFA0501100 and 2017YFA0504600 to M.J., and 2016YFA0500700 and 2013CB910400 to N.G.), and the National Fund for Distinguished Young Scholar (31625008 to M.Y.) and National Natural Science Foundation of China (Grant Nos. 21532004 and 31570733 to M.Y., 31422016 to N.G., 31371066 and 31671049 to Y.L., and 91426302 to J.L.)

  • Received Date: 2017-07-02
  • Rev Recd Date: 2017-08-02
  • Mechanosensitive (MS) channels are extensively studied membrane protein for maintaining intracellular homeostasis through translocating solutes and ions across the membrane, but its mechanisms of channel gating and ion selectivity are largely unknown. Here, we identified the YnaI channel as the Na+/K+ cation-selective MS channel and solved its structure at 3.8 Å by cryoEM single-particle method. YnaI exhibits low conductance among the family of MS channels in E. coli, and shares a similar overall heptamer structure fold with previously studied MscS channels. By combining structural based mutagenesis, quantum mechanical and electrophysiological characterizations, we revealed that ion selective filter formed by seven hydrophobic methionine (YnaIMet158) in the transmembrane pore determined ion selectivity, and both ion selectivity and gating of YnaI channel were affected by accompanying anions in solution. Further quantum simulation and functional validation support that the distinct binding energies with various anions to YnaIMet158 facilitate Na+/K+ pass through, which was defined as bindingblock mechanism. Our structural and functional studies provided a new perspective for understanding the mechanism of how MS channels select ions driven by mechanical force.
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