钠通道
结构生物学
离子通道
钙
生物物理学
化学
钙信号传导
电压依赖性钙通道
分子药理学
跨膜蛋白
钠
神经科学
生物
生物化学
信号转导
受体
有机化学
作者
William A. Catterall,Michael J. Lenaeus,Tamer M. Gamal El-Din
出处
期刊:Annual Review of Pharmacology and Toxicology
[Annual Reviews]
日期:2020-01-06
卷期号:60 (1): 133-154
被引量:198
标识
DOI:10.1146/annurev-pharmtox-010818-021757
摘要
Voltage-gated sodium and calcium channels are evolutionarily related transmembrane signaling proteins that initiate action potentials, neurotransmission, excitation-contraction coupling, and other physiological processes. Genetic or acquired dysfunction of these proteins causes numerous diseases, termed channelopathies, and sodium and calcium channels are the molecular targets for several major classes of drugs. Recent advances in the structural biology of these proteins using X-ray crystallography and cryo-electron microscopy have given new insights into the molecular basis for their function and pharmacology. Here we review this recent literature and integrate findings on sodium and calcium channels to reveal the structural basis for their voltage-dependent activation, fast and slow inactivation, ion conductance and selectivity, and complex pharmacology at the atomic level. We conclude with the theme that new understanding of the diseases and therapeutics of these channels will be derived from application of the emerging structural principles from these recent structural analyses.
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