The structural basis of divalent cation block in a tetrameric prokaryotic sodium channel
Abstract Divalent cation block is observed in various tetrameric ion channels. For blocking, a divalent cation is thought to bind in the ion pathway of the channel, but such block has not yet been directly observed. So, the behaviour of these blocking divalent cations remains still uncertain. Here,...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-39987-0 |
| _version_ | 1797778820701356032 |
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| author | Katsumasa Irie Yoshinori Oda Takashi Sumikama Atsunori Oshima Yoshinori Fujiyoshi |
| author_facet | Katsumasa Irie Yoshinori Oda Takashi Sumikama Atsunori Oshima Yoshinori Fujiyoshi |
| author_sort | Katsumasa Irie |
| collection | DOAJ |
| description | Abstract Divalent cation block is observed in various tetrameric ion channels. For blocking, a divalent cation is thought to bind in the ion pathway of the channel, but such block has not yet been directly observed. So, the behaviour of these blocking divalent cations remains still uncertain. Here, we elucidated the mechanism of the divalent cation block by reproducing the blocking effect into NavAb, a well-studied tetrameric sodium channel. Our crystal structures of NavAb mutants show that the mutations increasing the hydrophilicity of the inner vestibule of the pore domain enable a divalent cation to stack on the ion pathway. Furthermore, non-equilibrium molecular dynamics simulation showed that the stacking calcium ion repel sodium ion at the bottom of the selectivity filter. These results suggest the primary process of the divalent cation block mechanism in tetrameric cation channels. |
| first_indexed | 2024-03-12T23:22:05Z |
| format | Article |
| id | doaj.art-379e5ac02ce046029f3077e191bc3d10 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-12T23:22:05Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-379e5ac02ce046029f3077e191bc3d102023-07-16T11:20:47ZengNature PortfolioNature Communications2041-17232023-07-0114111210.1038/s41467-023-39987-0The structural basis of divalent cation block in a tetrameric prokaryotic sodium channelKatsumasa Irie0Yoshinori Oda1Takashi Sumikama2Atsunori Oshima3Yoshinori Fujiyoshi4Department of Biophysical Chemistry, School of Pharmaceutical Sciences, Wakayama Medical UniversityDepartment of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, ChikusaPRESTO, JSTCellular and Structural Physiology Institute (CeSPI), Nagoya University, Furo-cho, ChikusaCellular and Structural Physiology Laboratory (CeSPL), Advanced Research Institute, Tokyo Medical and Dental UniversityAbstract Divalent cation block is observed in various tetrameric ion channels. For blocking, a divalent cation is thought to bind in the ion pathway of the channel, but such block has not yet been directly observed. So, the behaviour of these blocking divalent cations remains still uncertain. Here, we elucidated the mechanism of the divalent cation block by reproducing the blocking effect into NavAb, a well-studied tetrameric sodium channel. Our crystal structures of NavAb mutants show that the mutations increasing the hydrophilicity of the inner vestibule of the pore domain enable a divalent cation to stack on the ion pathway. Furthermore, non-equilibrium molecular dynamics simulation showed that the stacking calcium ion repel sodium ion at the bottom of the selectivity filter. These results suggest the primary process of the divalent cation block mechanism in tetrameric cation channels.https://doi.org/10.1038/s41467-023-39987-0 |
| spellingShingle | Katsumasa Irie Yoshinori Oda Takashi Sumikama Atsunori Oshima Yoshinori Fujiyoshi The structural basis of divalent cation block in a tetrameric prokaryotic sodium channel Nature Communications |
| title | The structural basis of divalent cation block in a tetrameric prokaryotic sodium channel |
| title_full | The structural basis of divalent cation block in a tetrameric prokaryotic sodium channel |
| title_fullStr | The structural basis of divalent cation block in a tetrameric prokaryotic sodium channel |
| title_full_unstemmed | The structural basis of divalent cation block in a tetrameric prokaryotic sodium channel |
| title_short | The structural basis of divalent cation block in a tetrameric prokaryotic sodium channel |
| title_sort | structural basis of divalent cation block in a tetrameric prokaryotic sodium channel |
| url | https://doi.org/10.1038/s41467-023-39987-0 |
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