a Chemistry Teaching Center, College of Chemistry and Biology , Beihua University , Jilin , People's Republic of China.
b The Fungal Reference Laboratory of Shanghai Dermatology Hospital , Shanghai , China.
J Biomol Struct Dyn. 2018 Aug;36(10):2558-2566. doi: 10.1080/07391102.2017.1363087. Epub 2017 Aug 24.
Acid-sensing ion channel 1a (ASIC1a) is a cation channel activated by protons and causes neuronal death through central nervous system. Psalmotoxin1 (PcTx1) is a gating modifier for ASIC1a. The process of PcTx1 regulating the channel gating from the extracellular domain to the transmembrane domain is unclear. Here we used molecular dynamics (MD) simulations method to investigate how PcTx1 regulates the gating of the ASIC1a. Our results indicated that PcTx1can mainly regulate ASIC1a gating process through hydrogen bonds, which can affect their relative positions of several key domains in ASIC1a, further, a long-range conformational changes path was determined, which is composed of β1, β2, β10, α6, α7, β11, and β12 in ASIC1a.
酸敏离子通道 1a（ASIC1a）是一种被质子激活的阳离子通道，通过中枢神经系统导致神经元死亡。Psalmotoxin1（PcTx1）是 ASIC1a 的门控修饰物。PcTx1 从细胞外域调节通道门控到跨膜域的过程尚不清楚。在这里，我们使用分子动力学（MD）模拟方法来研究 PcTx1 如何调节 ASIC1a 的门控。我们的结果表明，PcTx1 主要可以通过氢键调节 ASIC1a 的门控过程，这可以影响 ASIC1a 中几个关键结构域的相对位置，进一步确定了一个长程构象变化路径，该路径由 ASIC1a 中的β1、β2、β10、α6、α7、β11 和β12 组成。
