Structure-based assessment of disease-related mutations in human voltage-gated sodium channels. Issue 6 (1st February 2017)

• Record Type: Journal Article
• Authors: Huang, Weiyun; Liu, Minhao; Yan, S Frank; Yan, Nieng
• Is Part Of: Protein & cell. Volume 8:Issue 6(2017)
• Page Start: 401
• Page End: 438
• Publication Date: 2017-02-01
• Subjects: Nav channels -- channelopathy -- Nav1.7 -- structure modeling -- pain; Proteins -- Periodicals; Cells -- Periodicals; Cytology -- Periodicals; 572.6
• DOI: 10.1007/s13238-017-0372-z
• Languages: English
• ISSNs: 1674-800X

Abstract

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 Nav 1.1 and Nav 1.5 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 Cav 1.1 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 Nav 1.7, 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.