Sarcolipin (SLN) is an important transmembrane (TM) protein encoded by long noncoding RNA. SLN is expressed in the sarcoplasmic reticulum and regulates cardiac and skeletal muscle contractions. SLN forms a pentameric hydrophobic ligand‐gated ion channel. The protonation of Glu7 (protonated SLN, pSLN) and mutation of Thr18 to Ala18 (T18A) have been reported to exert a significant influence on the permeability of the channel. In this study, the altered permeability of both the pSLN and T18A pentameric channels was simulated. Combined with molecular dynamics simulation, the free‐energy landscape for single ions, computational electrophysiology, diffusion coefficient, and pore geometrical characteristic analyses were performed to further understand the properties of amino acid modifications in the SLN pentameric channel. The results suggest that both the pSLN and T18A pentameric channels form stable hydrophobic ligand‐gated channels. The TM voltage has a positive effect on the permeability of water molecules and ions. By using pSLN and T18A, our study provides helpful information on the pore‐forming mechanism of SLN and furthers our understanding of the regulatory mechanisms underlying the permeation of ions and water molecules in the pentameric SLN channel.

中文翻译：

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氨基酸修饰对五聚体肌磷脂通道通透性的影响

Sarcolipin (SLN) 是一种重要的跨膜 (TM) 蛋白，由长链非编码 RNA 编码。SLN 在肌浆网中表达并调节心脏和骨骼肌收缩。SLN 形成五聚体疏水配体门控离子通道。据报道，Glu7 质子化（质子化 SLN，pSLN）和 Thr18 突变为 Ala18（T18A）对通道的通透性产生显着影响。在这项研究中，模拟了 pSLN 和 T18A 五聚体通道的通透性改变。结合分子动力学模拟，对单离子的自由能图、计算电生理学、扩散系数和孔几何特征进行了分析，以进一步了解 SLN 五聚体通道中氨基酸修饰的特性。结果表明 pSLN 和 T18A 五聚体通道均形成稳定的疏水性配体门控通道。TM 电压对水分子和离子的渗透性有积极影响。通过使用 pSLN 和 T18A，我们的研究提供了有关 SLN 成孔机制的有用信息，并进一步了解了离子和水分子在五聚体 SLN 通道中渗透的调控机制。