The crystal structure of human chloride intracellular channel protein 2: A disulfide bond with functional implications
The crystal structure of human chloride intracellular channel protein 2: A disulfide bond with functional implications
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DOI：
10.1002/prot.21922
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发表时间：
2008-04-01
影响因子：
2.9
通讯作者：
Su, Xiao-Dong
中科院分区：
文献类型：
--
作者：
Mi, Wei;Liang, Yu-He;Su, Xiao-Dong
人氯细胞内通道蛋白 (CLIC) 是基于序列同源性的细胞内离子通道。人类 CLIC 包括 6 个成员（CLIC1-6），它们都包含约 240 个氨基酸的保守核心。 CLIC最显着的特征是它们可以以两种状态存在：可溶性胞质状态和完整膜离子通道状态。纯化的水溶性 CLIC 采用谷胱甘肽 S-转移酶 (GST) 折叠，可以插入脂质膜形成氯离子通道。 1, 2 在人类 CLIC 中，CLIC1 和 CLIC4 已得到充分研究，并已解析晶体结构。 1,3,4 CLIC1和CLIC4在调节细胞周期、细胞凋亡等方面具有重要功能，已成为癌症治疗的潜在药物靶点。 5–8 人类 CLIC2 的分子量为 28.4 kDa，计算等电点为 5.44。 CLIC2基因位于Xq28的端粒区域，由6个编码外显子和5个内含子组成。由于X染色体的这个区域与许多遗传性疾病密切相关，因此CLIC2被提议作为与Xq28相关的一些遗传性疾病的候选基因。 9 Northern blot证明CLIC2基因可以在肺、脾、心脏和骨骼肌中表达。 10 与 CLIC1 或 CLIC4 相比，迄今为止对 CLIC2 的功能了解还很少。 CLIC2 唯一有记录的功能是调节心脏钙离子通道兰尼碱受体 2 (RyR2)。 11 在这项工作中，我们展示了人 CLIC2 可溶形式的晶体结构，并试图将一些结构特征与其潜在功能相关联。
Human chloride intracellular channel proteins (CLICs) are intracellular ion channels based on sequence homology. Human CLICs include six members (CLIC1-6), and all of them contain a conserved core about 240 amino acids. The most distinct feature of CLICs is that they can exist in two states: the soluble cytosolic state and the integral membrane ion channel state. Purified water-soluble CLICs adopt the glutathione S-transferase (GST) fold and can insert into a lipid membrane to form chloride channel. 1, 2 Among the human CLICs, CLIC1 and CLIC4 have been well studied with the crystal structures solved. 1, 3, 4 The CLIC1 and CLIC4 have important functions in regulating cell cycle, apoptosis, and so forth, and have become potential drug targets for cancer therapy. 5–8 Human CLIC2 has a molecular weight of 28.4 kDa and a calculated isoelectric point of 5.44. The CLIC2 gene locates in the telomeric region of Xq28 and is composed of six coding exons and five introns. Since this region of the X chromosome is closely associated with many hereditary diseases, CLIC2 has thus been proposed as a candidate gene for some genetic disorders linked to Xq28. 9 Northern blot has demonstrated that the gene of CLIC2 could be expressed in lung, spleen, heart, and skeletal muscle. 10 Compared with the CLIC1 or CLIC4, little functional knowledge is known about CLIC2 so far. The only documented function of CLIC2 is to regulate the cardiac calcium ion channel, ryanodine receptor 2 (RyR2). 11 In this work, we present the crystal structure of the soluble form of human CLIC2 and tried to correlate some structural features to its potential function.