Villanelo Felipe, Carrasco Jorge, Jensen-Flores Joaquin, Garate Jose Antonio, Perez-Acle Tomas
Computational Biology Laboratory, Fundación Ciencia & Vida, Zañartu 1482, Ñuñoa, Santiago 7780132, Chile.
Facultad de Ingeniería y Tecnología, Universidad San Sebastián, Santiago 8420524, Chile.
Membranes (Basel). 2021 May 20;11(5):372. doi: 10.3390/membranes11050372.
Connexin hemichannels allow the unspecific but regulated interchange of molecules from ions to second messenger and ATP, between the eukariotic cell and its extracellular space. The transport of ions and water through hemichannels is important for physiological functions and also in the progression of several pathological conditions. Extracellular Ca concentration is one of the regulators that drives the channel to a closed state. However the relation between their functional and structural states is far for being totally understood. In this work, we modelled connexin hemichannels using simple systems based on a fixed array of carbon atoms and assess the Ca regulation using molecular dynamics simulations. The two proposed mechanism described so far for calcium action were studied combined, e.g., an electrostatic effect and a pore stretching. Our results show that the addition of positive charge density inside the channel cannot stop the flow of potassium, chloride nor water. Only a pore stretching at the center of the pore can explain the channel blocking.
连接蛋白半通道允许真核细胞与其细胞外空间之间进行从离子到第二信使和ATP等分子的非特异性但受调控的交换。离子和水通过半通道的运输对生理功能以及几种病理状况的发展都很重要。细胞外钙浓度是驱动通道进入关闭状态的调节因子之一。然而，它们的功能状态和结构状态之间的关系远未被完全理解。在这项工作中，我们使用基于固定碳原子阵列的简单系统对连接蛋白半通道进行建模，并使用分子动力学模拟评估钙调节。对迄今为止描述的钙作用的两种提出的机制进行了联合研究，例如，静电效应和孔拉伸。我们的结果表明，在通道内部增加正电荷密度并不能阻止钾、氯和水的流动。只有孔中心的孔拉伸才能解释通道阻塞。
