The calcium permeation mechanism of the ryanodine receptor revealed by a multi-site ion model
The calcium permeation mechanism of the ryanodine receptor revealed by a multi-site ion model
复制标题
多位点离子模型揭示兰尼碱受体的钙渗透机制
DOI：
10.1038/s41467-020-14573-w
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发表时间：
2020
影响因子：
16.6
通讯作者：
Song Chen
中科院分区：
文献类型：
--
作者：
Zhang Aihua;Yu Hua;Liu Chunhong;Song Chen
Ryanodine receptor （RyR）是一种离子通道，负责Ca2+从sarco/内质网释放，并在胞浆中Ca2+浓度的精确控制中起着至关重要的作用。Ca2+通过RyR的具体渗透机制尚不清楚。通过使用分子动力学模拟与专门设计的Ca2+模型，我们表明，多个Ca2+离子积累在RyR1的高选择性过滤器，但只有一个Ca2+可以占据和转运在狭窄的孔中，在静电排斥的帮助下，从高选择性过滤器内的Ca2+。在整个渗透过程中，Ca2+几乎完全水化，第一溶剂化壳完整。这些结果表明了水合Ca2+在窄孔内的远程连锁渗透机制和一次占领模式，揭示了RyR通道高渗透性和低选择性的基础。
Ryanodine receptors (RyR) are ion channels responsible for the release of Ca2+from the sarco/endoplasmic reticulum and play a crucial role in the precise control of Ca2+concentration in the cytosol. The detailed permeation mechanism of Ca2+through RyR is still elusive. By using molecular dynamics simulations with a specially designed Ca2+model, we show that multiple Ca2+ions accumulate in the upper selectivity filter of RyR1, but only one Ca2+can occupy and translocate in the narrow pore at a time, assisted by electrostatic repulsion from the Ca2+within the upper selectivity filter. The Ca2+is nearly fully hydrated with the first solvation shell intact during the whole permeation process. These results suggest a remote knock-on permeation mechanism and one-at-a-time occupation pattern for the hydrated Ca2+within the narrow pore, uncovering the basis underlying the high permeability and low selectivity of the RyR channels.