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Protein Cell. 2018 Jul;9(7):629-639. doi: 10.1007/s13238-017-0465-8. Epub 2017 Sep 18.

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

Author information

1
Ministry of Education Key Laboratory of Protein Science, School of Life Sciences, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing, 100084, China.
2
Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
3
University of Chinese Academy of Sciences, Beijing, 100049, China.
4
Anesthesiology, Shanghai First Maternity and Infant Hospital, Tongji University school of Medicine, Shanghai, 201203, China.
5
Department of Chemistry and Key Laboratory of Organic Optoelectronics and Molecular Engineering of the Ministry of Education, Tsinghua University, Beijing, 100084, China.
6
Ministry of Education Key Laboratory of Protein Science, School of Life Sciences, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing, 100084, China. gaon@pku.edu.cn.
7
Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. Liyang@simm.ac.cn.
8
Ministry of Education Key Laboratory of Protein Science, School of Life Sciences, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing, 100084, China. maojunyang@tsinghua.edu.cn.

Abstract

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 cryo-EM 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 binding-block mechanism. Our structural and functional studies provided a new perspective for understanding the mechanism of how MS channels select ions driven by mechanical force.

KEYWORDS:

MscS; Na+/K+ selective channel; cryo-EM

PMID:
28921397
PMCID:
PMC6019658
DOI:
10.1007/s13238-017-0465-8
[Indexed for MEDLINE]
Free PMC Article

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