动物多肽与钠通道选择性互作的微基序空间等电点

Micromotifs and Spatial Isoelectric Point for Selective Interaction between Animal Peptides and Sodium Channels

电压门控钠通道(Voltage-gated sodium channels,Nav,钠通道)是产生和传播神经冲动的重要离子通道,是动物多肽类毒素靶通道之一。动物多肽结合不同的钠通道受体位点,改变Nav的构象和通道动力学特性。本文聚焦钠通道与动物多肽的功能性结合,以经典动物多肽AaH2、Protoxin-II与Nav1.7互作的冷冻电镜颗粒结构为模板,探究多肽结合与钠通道激活、失活相关的电压感受器构象变化,提出多肽与钠通道互作的微结构域、氨基酸基序和空间等电点效价模型,以期为新型钠通道亚型特异性人工肽的设计和研制提供新思路。

Voltage-gated sodium channels(Nav)are most important for generation and transmission of action potential in excitatory cells and specific targets of animal peptides,which bind to distinct receptor sites of Nav and thus modulate channel gating and conformation.Based on the single particle cryo electron microscopy,this paper focused on the functional interaction between classical animal peptide scorpion AaH2,spider Protoxin-II and sodium channel Nav1.7,and uncovered the conformation changes associated with the dynamic activation,inactivation of Nav voltage sensor.Furthermore,several novel models of micro domain,micro amino acid motif and spatial isoelectric point for the selective interaction between animal peptides and sodium channels were proposed,in order to provide some strategies for the design and development of new sodium channel subtype specific artificial peptides.