The P2X receptor is a trimeric transmembrane protein that acts as an ATP-gated ion channel. Its transmembrane domain (TMD) contains only six helices and three of them, the M2 helices, line the ion conduction pathway. Here, using molecular dynamics simulation, I identify four conformational states of the TMD that are associated with four types of packing between M2 helices. Packing in the extracellular half of the M2 helix produces closed conformations, while packing in the intracellular half produces both open and closed conformations. State transition is observed and supports a mechanism where iris-like twisting of the M2 helices switches the location of helical packing between the extracellular and the intracellular halves of the helices. In addition, this twisting motion alters the position and orientation of residue side-chains relative to the pore and therefore influences the pore geometry and possibly ion permeation. Helical packing, on the other hand, may restrict the twisting motion and generate discrete conformational states.

中文翻译：

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通过分子动力学模拟探索 P2X 受体跨膜域的构象状态和螺旋堆积

P2X 受体是一种三聚体跨膜蛋白，充当 ATP 门控离子通道。它的跨膜结构域 (TMD) 仅包含六个螺旋，其中三个，即 M2 螺旋，排列在离子传导通路上。在这里，使用分子动力学模拟，我确定了与 M2 螺旋之间的四种类型的堆积相关的 TMD 的四种构象状态。填充在 M2 螺旋的细胞外半部产生闭合构象，而填充在细胞内半部则产生开放和闭合构象。观察到状态转换并支持一种机制，其中 M2 螺旋的虹膜状扭曲在螺旋的细胞外和细胞内一半之间切换螺旋堆积的位置。此外，这种扭曲运动改变了残留侧链相对于孔的位置和方向，因此影响了孔的几何形状和可能的离子渗透。另一方面，螺旋堆积可能会限制扭转运动并产生离散的构象状态。