Atomistic Details of Charge/Space Competition in the Ca2+ Selectivity of Ryanodine Receptors
Atomistic Details of Charge/Space Competition in the Ca2+ Selectivity of Ryanodine Receptors
复制标题
Ryanodine 受体 Ca2+ 选择性中电荷/空间竞争的原子细节
DOI：
10.1021/acs.jpclett.1c00681
复制
发表时间：
2021-04-28
影响因子：
5.7
通讯作者：
Song, Chen
中科院分区：
文献类型：
--
作者：
Liu, Chunhong;Zhang, Aihua;Song, Chen
Ryanodine受体（RyRs）是一种离子通道，负责Ca2+从sarco/内质网快速释放到细胞质，并表现出Ca2+对一价阳离子的选择性。通过在分子动力学模拟中利用最近开发的多位点Ca2+模型，我们发现多个阳离子在ryr的高选择性过滤器中积累，并且Ca2+的小尺寸和高价使其在负静电势的有限区域内竞争空间时优于K+。高选择性滤膜中Ca2+的存在显著增加了K+渗透的能量势垒，而K+的存在对Ca2+渗透的影响不大。我们的研究结果提供了ryr离子选择性的电荷/空间竞争机制的原子细节，这确保了它们的Ca2+释放功能的鲁棒性。该机制可用于蛋白质和纳米工程中离子的价选择性。
Ryanodine receptors (RyRs) are ion channels responsible for the fast release of Ca2+ from the sarco/endoplasmic reticulum to the cytosol and show a selectivity of Ca2+ over monovalent cations. By utilizing a recently developed multisite Ca2+ model in molecular dynamic simulations, we show that multiple cations accumulate in the upper selectivity filter of RyRs, and the small size and high valence of Ca2+ make it preferable to K+ in competition for space in this confined region of negative electrostatic potential. The presence of Ca2+ in the upper selectivity filter significantly increases the energy barrier of K+ permeation, while the presence of K+ has little impact on the Ca2+ permeation. Our results provide the atomistic details of the charge/space competition mechanism for the ion selectivity of RyRs, which ensures the robustness of their Ca2+ release function. The mechanism could be utilized in protein- and nanoengineering for valence selectivity of ion species.