Structure of the human voltage-gated sodium channel Nav1.4 in complex with {beta}1
Pan, X., Li, Z., Zhou, Q., Shen, H., Wu, K., Huang, X., Chen, J., Zhang, J., Zhu, X., Lei, J., Xiong, W., Gong, H., Xiao, B., Yan, N.
American Association for the Advancement of Science (AAAS)
Published 2018
American Association for the Advancement of Science (AAAS)
Published 2018
| Publication Date: |
2018-10-19
|
|---|---|
| Publisher: |
American Association for the Advancement of Science (AAAS)
|
| Print ISSN: |
0036-8075
|
| Electronic ISSN: |
1095-9203
|
| Topics: |
Biology
Chemistry and Pharmacology
Geosciences
Computer Science
Medicine
Natural Sciences in General
Physics
|
| Keywords: |
Molecular Biology, Online Only
|
| Published by: |
| _version_ | 1839208209238196224 |
|---|---|
| autor | Pan, X., Li, Z., Zhou, Q., Shen, H., Wu, K., Huang, X., Chen, J., Zhang, J., Zhu, X., Lei, J., Xiong, W., Gong, H., Xiao, B., Yan, N. |
| beschreibung | Voltage-gated sodium (Na v ) channels, which are responsible for action potential generation, are implicated in many human diseases. Despite decades of rigorous characterization, the lack of a structure of any human Na v channel has hampered mechanistic understanding. Here, we report the cryo–electron microscopy structure of the human Na v 1.4-β1 complex at 3.2-Å resolution. Accurate model building was made for the pore domain, the voltage-sensing domains, and the β1 subunit, providing insight into the molecular basis for Na + permeation and kinetic asymmetry of the four repeats. Structural analysis of reported functional residues and disease mutations corroborates an allosteric blocking mechanism for fast inactivation of Na v channels. The structure provides a path toward mechanistic investigation of Na v channels and drug discovery for Na v channelopathies. |
| citation_standardnr | 6346590 |
| datenlieferant | ipn_articles |
| feed_id | 25 |
| feed_publisher | American Association for the Advancement of Science (AAAS) |
| feed_publisher_url | http://www.aaas.org/ |
| insertion_date | 2018-10-19 |
| journaleissn | 1095-9203 |
| journalissn | 0036-8075 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | American Association for the Advancement of Science (AAAS) |
| quelle | Science |
| relation | http://science.sciencemag.org/cgi/content/short/362/6412/eaau2486?rss=1 |
| schlagwort | Molecular Biology, Online Only |
| search_space | articles |
| shingle_author_1 | Pan, X., Li, Z., Zhou, Q., Shen, H., Wu, K., Huang, X., Chen, J., Zhang, J., Zhu, X., Lei, J., Xiong, W., Gong, H., Xiao, B., Yan, N. |
| shingle_author_2 | Pan, X., Li, Z., Zhou, Q., Shen, H., Wu, K., Huang, X., Chen, J., Zhang, J., Zhu, X., Lei, J., Xiong, W., Gong, H., Xiao, B., Yan, N. |
| shingle_author_3 | Pan, X., Li, Z., Zhou, Q., Shen, H., Wu, K., Huang, X., Chen, J., Zhang, J., Zhu, X., Lei, J., Xiong, W., Gong, H., Xiao, B., Yan, N. |
| shingle_author_4 | Pan, X., Li, Z., Zhou, Q., Shen, H., Wu, K., Huang, X., Chen, J., Zhang, J., Zhu, X., Lei, J., Xiong, W., Gong, H., Xiao, B., Yan, N. |
| shingle_catch_all_1 | Structure of the human voltage-gated sodium channel Nav1.4 in complex with {beta}1 Molecular Biology, Online Only Voltage-gated sodium (Na v ) channels, which are responsible for action potential generation, are implicated in many human diseases. Despite decades of rigorous characterization, the lack of a structure of any human Na v channel has hampered mechanistic understanding. Here, we report the cryo–electron microscopy structure of the human Na v 1.4-β1 complex at 3.2-Å resolution. Accurate model building was made for the pore domain, the voltage-sensing domains, and the β1 subunit, providing insight into the molecular basis for Na + permeation and kinetic asymmetry of the four repeats. Structural analysis of reported functional residues and disease mutations corroborates an allosteric blocking mechanism for fast inactivation of Na v channels. The structure provides a path toward mechanistic investigation of Na v channels and drug discovery for Na v channelopathies. Pan, X., Li, Z., Zhou, Q., Shen, H., Wu, K., Huang, X., Chen, J., Zhang, J., Zhu, X., Lei, J., Xiong, W., Gong, H., Xiao, B., Yan, N. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_catch_all_2 | Structure of the human voltage-gated sodium channel Nav1.4 in complex with {beta}1 Molecular Biology, Online Only Voltage-gated sodium (Na v ) channels, which are responsible for action potential generation, are implicated in many human diseases. Despite decades of rigorous characterization, the lack of a structure of any human Na v channel has hampered mechanistic understanding. Here, we report the cryo–electron microscopy structure of the human Na v 1.4-β1 complex at 3.2-Å resolution. Accurate model building was made for the pore domain, the voltage-sensing domains, and the β1 subunit, providing insight into the molecular basis for Na + permeation and kinetic asymmetry of the four repeats. Structural analysis of reported functional residues and disease mutations corroborates an allosteric blocking mechanism for fast inactivation of Na v channels. The structure provides a path toward mechanistic investigation of Na v channels and drug discovery for Na v channelopathies. Pan, X., Li, Z., Zhou, Q., Shen, H., Wu, K., Huang, X., Chen, J., Zhang, J., Zhu, X., Lei, J., Xiong, W., Gong, H., Xiao, B., Yan, N. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_catch_all_3 | Structure of the human voltage-gated sodium channel Nav1.4 in complex with {beta}1 Molecular Biology, Online Only Voltage-gated sodium (Na v ) channels, which are responsible for action potential generation, are implicated in many human diseases. Despite decades of rigorous characterization, the lack of a structure of any human Na v channel has hampered mechanistic understanding. Here, we report the cryo–electron microscopy structure of the human Na v 1.4-β1 complex at 3.2-Å resolution. Accurate model building was made for the pore domain, the voltage-sensing domains, and the β1 subunit, providing insight into the molecular basis for Na + permeation and kinetic asymmetry of the four repeats. Structural analysis of reported functional residues and disease mutations corroborates an allosteric blocking mechanism for fast inactivation of Na v channels. The structure provides a path toward mechanistic investigation of Na v channels and drug discovery for Na v channelopathies. Pan, X., Li, Z., Zhou, Q., Shen, H., Wu, K., Huang, X., Chen, J., Zhang, J., Zhu, X., Lei, J., Xiong, W., Gong, H., Xiao, B., Yan, N. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_catch_all_4 | Structure of the human voltage-gated sodium channel Nav1.4 in complex with {beta}1 Molecular Biology, Online Only Voltage-gated sodium (Na v ) channels, which are responsible for action potential generation, are implicated in many human diseases. Despite decades of rigorous characterization, the lack of a structure of any human Na v channel has hampered mechanistic understanding. Here, we report the cryo–electron microscopy structure of the human Na v 1.4-β1 complex at 3.2-Å resolution. Accurate model building was made for the pore domain, the voltage-sensing domains, and the β1 subunit, providing insight into the molecular basis for Na + permeation and kinetic asymmetry of the four repeats. Structural analysis of reported functional residues and disease mutations corroborates an allosteric blocking mechanism for fast inactivation of Na v channels. The structure provides a path toward mechanistic investigation of Na v channels and drug discovery for Na v channelopathies. Pan, X., Li, Z., Zhou, Q., Shen, H., Wu, K., Huang, X., Chen, J., Zhang, J., Zhu, X., Lei, J., Xiong, W., Gong, H., Xiao, B., Yan, N. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_title_1 | Structure of the human voltage-gated sodium channel Nav1.4 in complex with {beta}1 |
| shingle_title_2 | Structure of the human voltage-gated sodium channel Nav1.4 in complex with {beta}1 |
| shingle_title_3 | Structure of the human voltage-gated sodium channel Nav1.4 in complex with {beta}1 |
| shingle_title_4 | Structure of the human voltage-gated sodium channel Nav1.4 in complex with {beta}1 |
| timestamp | 2025-07-31T23:47:11.057Z |
| titel | Structure of the human voltage-gated sodium channel Nav1.4 in complex with {beta}1 |
| titel_suche | Structure of the human voltage-gated sodium channel Nav1.4 in complex with {beta}1 |
| topic | W V TE-TZ SQ-SU WW-YZ TA-TD U |
| uid | ipn_articles_6346590 |