Structure-based assessment of disease-related mutations in human voltage-gated sodium channels
ABSTRACT Voltage-gated sodium (Nav) channels are essential for the rapid upstroke of action potentials and the propagation of electrical signals in nerves and muscles. Defects of Nav channels are associated with a variety of channelopathies. More than 1000 disease-related mutations have been identif...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Oxford University Press
2017-02-01
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| Series: | Protein & Cell |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1007/s13238-017-0372-z |
| _version_ | 1797707125581938688 |
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| author | Weiyun Huang Minhao Liu S. Frank Yan Nieng Yan |
| author_facet | Weiyun Huang Minhao Liu S. Frank Yan Nieng Yan |
| author_sort | Weiyun Huang |
| collection | DOAJ |
| description | ABSTRACT Voltage-gated sodium (Nav) channels are essential for the rapid upstroke of action potentials and the propagation of electrical signals in nerves and muscles. Defects of Nav channels are associated with a variety of channelopathies. More than 1000 disease-related mutations have been identified in Nav channels, with Nav1.1 and Nav1.5 each harboring more than 400 mutations. Nav channels represent major targets for a wide array of neurotoxins and drugs. Atomic structures of Nav channels are required to understand their function and disease mechanisms. The recently determined atomic structure of the rabbit voltage-gated calcium (Cav) channel Cav1.1 provides a template for homology-based structural modeling of the evolutionarily related Nav channels. In this Resource article, we summarized all the reported disease-related mutations in human Nav channels, generated a homologous model of human Nav1.7, and structurally mapped disease-associated mutations. Before the determination of structures of human Nav channels, the analysis presented here serves as the base framework for mechanistic investigation of Nav channelopathies and for potential structure-based drug discovery. |
| first_indexed | 2024-03-12T06:02:45Z |
| format | Article |
| id | doaj.art-5d4a8ea6d31d437381718701307c1b97 |
| institution | Directory Open Access Journal |
| issn | 1674-800X 1674-8018 |
| language | English |
| last_indexed | 2024-03-12T06:02:45Z |
| publishDate | 2017-02-01 |
| publisher | Oxford University Press |
| record_format | Article |
| series | Protein & Cell |
| spelling | doaj.art-5d4a8ea6d31d437381718701307c1b972023-09-03T04:00:10ZengOxford University PressProtein & Cell1674-800X1674-80182017-02-018640143810.1007/s13238-017-0372-zStructure-based assessment of disease-related mutations in human voltage-gated sodium channelsWeiyun Huang0Minhao Liu1S. Frank Yan2Nieng Yan3State Key Laboratory of Membrane Biology, School of Life Sciences and School of Medicine, Tsinghua UniversityBeijing Advanced Innovation Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua UniversityMolecular Design and Chemical Biology, Roche Pharma Research and Early Development, Roche Innovation Center ShanghaiState Key Laboratory of Membrane Biology, School of Life Sciences and School of Medicine, Tsinghua UniversityABSTRACT Voltage-gated sodium (Nav) channels are essential for the rapid upstroke of action potentials and the propagation of electrical signals in nerves and muscles. Defects of Nav channels are associated with a variety of channelopathies. More than 1000 disease-related mutations have been identified in Nav channels, with Nav1.1 and Nav1.5 each harboring more than 400 mutations. Nav channels represent major targets for a wide array of neurotoxins and drugs. Atomic structures of Nav channels are required to understand their function and disease mechanisms. The recently determined atomic structure of the rabbit voltage-gated calcium (Cav) channel Cav1.1 provides a template for homology-based structural modeling of the evolutionarily related Nav channels. In this Resource article, we summarized all the reported disease-related mutations in human Nav channels, generated a homologous model of human Nav1.7, and structurally mapped disease-associated mutations. Before the determination of structures of human Nav channels, the analysis presented here serves as the base framework for mechanistic investigation of Nav channelopathies and for potential structure-based drug discovery.http://link.springer.com/article/10.1007/s13238-017-0372-zNav channelschannelopathyNav1.7structure modelingpain |
| spellingShingle | Weiyun Huang Minhao Liu S. Frank Yan Nieng Yan Structure-based assessment of disease-related mutations in human voltage-gated sodium channels Protein & Cell Nav channels channelopathy Nav1.7 structure modeling pain |
| title | Structure-based assessment of disease-related mutations in human voltage-gated sodium channels |
| title_full | Structure-based assessment of disease-related mutations in human voltage-gated sodium channels |
| title_fullStr | Structure-based assessment of disease-related mutations in human voltage-gated sodium channels |
| title_full_unstemmed | Structure-based assessment of disease-related mutations in human voltage-gated sodium channels |
| title_short | Structure-based assessment of disease-related mutations in human voltage-gated sodium channels |
| title_sort | structure based assessment of disease related mutations in human voltage gated sodium channels |
| topic | Nav channels channelopathy Nav1.7 structure modeling pain |
| url | http://link.springer.com/article/10.1007/s13238-017-0372-z |
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