Structural insights into transmembrane helix S0 facilitated RyR1 channel gating by Ca2+/ATP
Abstract The type-1 ryanodine receptor (RyR1) is an intracellular calcium release channel for skeletal muscle excitation-contraction coupling. Previous structural studies showed that the RyR1 activity is modulated by the exogenous regulators including caffeine, ryanodine, PCB-95 and diamide. An addi...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-57074-4 |
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| author | Risheng Wei Qiang Chen Lei Zhang Congcong Liu Chuang Liu Chang-Cheng Yin Hongli Hu |
| author_facet | Risheng Wei Qiang Chen Lei Zhang Congcong Liu Chuang Liu Chang-Cheng Yin Hongli Hu |
| author_sort | Risheng Wei |
| collection | DOAJ |
| description | Abstract The type-1 ryanodine receptor (RyR1) is an intracellular calcium release channel for skeletal muscle excitation-contraction coupling. Previous structural studies showed that the RyR1 activity is modulated by the exogenous regulators including caffeine, ryanodine, PCB-95 and diamide. An additional transmembrane helix, located adjacent to S1 and S4, has been observed in some structures, although its function remains unclear. Here, we report that using a mild purification procedure, this helix is co-purified with RyR1 and is designated as S0. When RyR1 is coupled with S0, it can be activated by Ca2+ to an open state; however when decoupled from S0, it remains in primed state. S0 regulates the channel conformation by directly affecting the TM domain via the pVSD-S0-S4/S5 linker coupling, which facilitates the dilation of S6. Our results demonstrate that S0 is an essential component of RyR1 and plays a key role in the physiological regulation of RyR1 channel gating. |
| format | Article |
| id | doaj-art-cf5e4ec787c4433d8c9bae9c4afbc7a6 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-cf5e4ec787c4433d8c9bae9c4afbc7a62025-08-20T03:04:07ZengNature PortfolioNature Communications2041-17232025-02-0116111010.1038/s41467-025-57074-4Structural insights into transmembrane helix S0 facilitated RyR1 channel gating by Ca2+/ATPRisheng Wei0Qiang Chen1Lei Zhang2Congcong Liu3Chuang Liu4Chang-Cheng Yin5Hongli Hu6Department of Biophysics, School of Basic Medical Sciences, Peking UniversityKobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen; ShenzhenElectron Microscopy Analysis Laboratory, Medical and Health Analysis Center, Peking UniversityInstitute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital; ShenzhenCenter for Biological Cryo-EM, Huazhong University of Science and TechnologyDepartment of Biophysics, School of Basic Medical Sciences, Peking UniversityKobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen; ShenzhenAbstract The type-1 ryanodine receptor (RyR1) is an intracellular calcium release channel for skeletal muscle excitation-contraction coupling. Previous structural studies showed that the RyR1 activity is modulated by the exogenous regulators including caffeine, ryanodine, PCB-95 and diamide. An additional transmembrane helix, located adjacent to S1 and S4, has been observed in some structures, although its function remains unclear. Here, we report that using a mild purification procedure, this helix is co-purified with RyR1 and is designated as S0. When RyR1 is coupled with S0, it can be activated by Ca2+ to an open state; however when decoupled from S0, it remains in primed state. S0 regulates the channel conformation by directly affecting the TM domain via the pVSD-S0-S4/S5 linker coupling, which facilitates the dilation of S6. Our results demonstrate that S0 is an essential component of RyR1 and plays a key role in the physiological regulation of RyR1 channel gating.https://doi.org/10.1038/s41467-025-57074-4 |
| spellingShingle | Risheng Wei Qiang Chen Lei Zhang Congcong Liu Chuang Liu Chang-Cheng Yin Hongli Hu Structural insights into transmembrane helix S0 facilitated RyR1 channel gating by Ca2+/ATP Nature Communications |
| title | Structural insights into transmembrane helix S0 facilitated RyR1 channel gating by Ca2+/ATP |
| title_full | Structural insights into transmembrane helix S0 facilitated RyR1 channel gating by Ca2+/ATP |
| title_fullStr | Structural insights into transmembrane helix S0 facilitated RyR1 channel gating by Ca2+/ATP |
| title_full_unstemmed | Structural insights into transmembrane helix S0 facilitated RyR1 channel gating by Ca2+/ATP |
| title_short | Structural insights into transmembrane helix S0 facilitated RyR1 channel gating by Ca2+/ATP |
| title_sort | structural insights into transmembrane helix s0 facilitated ryr1 channel gating by ca2 atp |
| url | https://doi.org/10.1038/s41467-025-57074-4 |
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