期刊
OPEN BIOLOGY
卷 5, 期 1, 页码 -出版社
ROYAL SOC
DOI: 10.1098/rsob.140192
关键词
sodium channel beta subunits; X-ray crystallography; ion channelopathies
资金
- Cambridge Nehru Trust scholarship
- Crystallographic X-ray Facility, Department of Biochemistry, University of Cambridge
- Medical Research Council (UK) [MR/M001288/1]
- MacVeigh Benefaction
- Alzheimers Research UK [ART-PPG2006B-4] Funding Source: researchfish
- Medical Research Council [MR/M001288/1] Funding Source: researchfish
- MRC [MR/M001288/1] Funding Source: UKRI
Voltage-gated sodium (Na-v) channels are intrinsic plasma membrane proteins that initiate the action potential in electrically excitable cells. They are a major focus of research in neurobiology, structural biology, membrane biology and pharmacology. Mutations in Na-v channels are implicated in a wide variety of inherited pathologies, including cardiac conduction diseases, myotonic conditions, epilepsy and chronic pain syndromes. Drugs active against Na-v channels are used as local anaesthetics, anti-arrhythmics, analgesics and anti-convulsants. The Na-v channels are composed of a pore-forming a subunit and associated beta subunits. The beta subunits are members of the immunoglobulin (Ig) domain family of cell-adhesion molecules. They modulate multiple aspects of Na-v channel behaviour and play critical roles in controlling neuronal excitability. The recently published atomic resolution structures of the human beta 3 and beta 4 subunit Ig domains open a new chapter in the study of these molecules. In particular, the discovery that beta 3 subunits form trimers suggests that Na-v channel oligomerization may contribute to the functional properties of some beta subunits.
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