Structure-based assessment of disease-related mutations in human voltage-gated sodium channels.

TitleStructure-based assessment of disease-related mutations in human voltage-gated sodium channels.
Publication TypeJournal Article
Year of Publication2017
AuthorsHuang, W, Liu, M, S Yan, F, Yan, N
JournalProtein Cell
Date Published2017 Jun
KeywordsAnimals, Calcium Channels, L-Type, Channelopathies, Humans, Mutation, NAV1.1 Voltage-Gated Sodium Channel, NAV1.5 Voltage-Gated Sodium Channel, NAV1.7 Voltage-Gated Sodium Channel, Protein Domains, Rabbits, Structure-Activity Relationship

<p>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.</p>

Alternate JournalProtein Cell
PubMed ID28150151
PubMed Central IDPMC5445024
Grant List / HHMI / Howard Hughes Medical Institute / United States