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首页> 外文期刊>Journal of Molecular Biology >CLIC2-RyR1 interaction and structural characterization by cryo-electron microscopy.
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CLIC2-RyR1 interaction and structural characterization by cryo-electron microscopy.

机译：CLIC2-RyR1相互作用和低温电子显微镜的结构表征。

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摘要

Chloride intracellular channel 2 (CLIC2), a newly discovered small protein distantly related to the glutathione transferase (GST) structural family, is highly expressed in cardiac and skeletal muscle, although its physiological function in these tissues has not been established. In the present study, [3H]ryanodine binding, Ca2+ efflux from skeletal sarcoplasmic reticulum (SR) vesicles, single channel recording, and cryo-electron microscopy were employed to investigate whether CLIC2 can interact with skeletal ryanodine receptor (RyR1) and modulate its channel activity. We found that: (1) CLIC2 facilitated [3H]ryanodine binding to skeletal SR and purified RyR1, by increasing the binding affinity of ryanodine for its receptor without significantly changing the apparent maximal binding capacity; (2) CLIC2 reduced the maximal Ca2+ efflux rate from skeletal SR vesicles; (3) CLIC2 decreased the open probability of RyR1 channel, through increasing the mean closed time of the channel; (4) CLIC2 bound to a region between domains 5 and 6 in the clamp-shaped region of RyR1; (5) and in the same clamp region, domains 9 and 10 became separated after CLIC2 binding, indicating CLIC2 induced a conformational change of RyR1. These data suggest that CLIC2 can interact with RyR1 and modulate its channel activity. We propose that CLIC2 functions as an intrinsic stabilizer of the closed state of RyR channels.
机译：氯化物细胞内通道2（CLIC2）是一种新发现的与谷胱甘肽转移酶（GST）结构家族密切相关的小蛋白，尽管在这些组织中尚未建立其生理功能，但在心肌和骨骼肌中却高度表达。在本研究中，[3H] ryanodine结合，骨骼肌质网（SR）囊泡中的Ca2 +流出，单通道记录和冷冻电子显微镜被用来研究CLIC2是否可以与骨骼肌ryanodine受体（RyR1）相互作用并调节其通道活动。我们发现：（1）CLIC2通过增加ryanodine与其受体的结合亲和力而没有明显改变表观最大结合能力，促进了[3H] ryanodine与骨骼SR的结合并纯化了RyR1。 （2）CLIC2降低了骨骼SR囊泡的最大Ca2 +外流率; （3）CLIC2通过增加通道的平均关闭时间来降低RyR1通道的打开概率; （4）CLIC2结合到RyR1的钳形区域中的结构域5和6之间的区域; （5）在相同的钳位区域中，域9和10在CLIC2结合后变得分离，表明CLIC2诱导了RyR1的构象变化。这些数据表明，CLIC2可以与RyR1相互作用并调节其通道活性。我们建议CLIC2充当RyR通道关闭状态的固有稳定剂。

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