Structure-based assessment of disease-related mutations in human voltage-gated sodium channels.
10.1007/s13238-017-0372-z
- Author:
Weiyun HUANG
1
;
Minhao LIU
2
;
S Frank YAN
3
;
Nieng YAN
4
Author Information
1. State Key Laboratory of Membrane Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, 100084, China.
2. Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, 100084, China.
3. Molecular Design and Chemical Biology, Roche Pharma Research and Early Development, Roche Innovation Center Shanghai, Shanghai, 201203, China. frank.yan@outlook.com.
4. State Key Laboratory of Membrane Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, 100084, China. nyan@tsinghua.edu.cn.
- Publication Type:Journal Article
- Keywords:
Nav channels;
Nav1.7;
channelopathy;
pain;
structure modeling
- MeSH:
Animals;
Calcium Channels, L-Type;
chemistry;
genetics;
metabolism;
Channelopathies;
genetics;
metabolism;
Humans;
Mutation;
NAV1.1 Voltage-Gated Sodium Channel;
chemistry;
genetics;
metabolism;
NAV1.5 Voltage-Gated Sodium Channel;
chemistry;
genetics;
metabolism;
NAV1.7 Voltage-Gated Sodium Channel;
chemistry;
genetics;
metabolism;
Protein Domains;
Rabbits;
Structure-Activity Relationship
- From:
Protein & Cell
2017;8(6):401-438
- CountryChina
- Language:English
-
Abstract:
Voltage-gated sodium (Na) channels are essential for the rapid upstroke of action potentials and the propagation of electrical signals in nerves and muscles. Defects of Na channels are associated with a variety of channelopathies. More than 1000 disease-related mutations have been identified in Na channels, with Na1.1 and Na1.5 each harboring more than 400 mutations. Na channels represent major targets for a wide array of neurotoxins and drugs. Atomic structures of Na channels are required to understand their function and disease mechanisms. The recently determined atomic structure of the rabbit voltage-gated calcium (Ca) channel Ca1.1 provides a template for homology-based structural modeling of the evolutionarily related Na channels. In this Resource article, we summarized all the reported disease-related mutations in human Na channels, generated a homologous model of human Na1.7, and structurally mapped disease-associated mutations. Before the determination of structures of human Na channels, the analysis presented here serves as the base framework for mechanistic investigation of Na channelopathies and for potential structure-based drug discovery.
