Cryo-EM structure of human Cx31.3/GJC3 connexin hemichannel
Cryo-EM structure of human Cx31.3/GJC3 connexin hemichannel
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DOI：
10.1126/sciadv.aba4996
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发表时间：
2020-08-01
期刊：
影响因子：
13.6
通讯作者：
Woo, Jae-Sung
中科院分区：
文献类型：
--
作者：
Lee, Hyuk-Joon;Jeong, Hyeongseop;Woo, Jae-Sung
连接蛋白家族蛋白组装成称为半通道/连接子的六聚体通道，其充当跨膜通道或对接在一起以形成间隙连接细胞间通道（GJIChs）。我们确定了冷冻电镜结构的人连接蛋白31.3（Cx31.3）/GJC 3半通道的存在和不存在的钙离子和听力损失突变R15 G在2.3-，2.5-和2.6埃的分辨率，分别。与开放构象的GJICh结构相比，Cx31.3半通道显示了连接蛋白家族中高度保守区域的实质性结构变化，包括钙离子结合隧道的开放、盐桥网络的重组、脂质结合位点的暴露以及氨基末端螺旋在胞质入口处的配置。我们还发现，半通道具有直径约为8埃的孔，并选择性地传输氯离子。我们的研究提供了对Cx31.3半通道的渗透选择性的结构见解。
Connexin family proteins assemble into hexameric channels called hemichannels/connexons, which function as transmembrane channels or dock together to form gap junction intercellular channels (GJIChs). We determined the cryo-electron microscopy structures of human connexin 31.3 (Cx31.3)/GJC3 hemichannels in the presence and absence of calcium ions and with a hearing-loss mutation R15G at 2.3-, 2.5-, and 2.6-angstrom resolutions, respectively. Compared with available structures of GJICh in open conformation, Cx31.3 hemichannel shows substantial structural changes of highly conserved regions in the connexin family, including opening of calcium ion-binding tunnels, reorganization of salt-bridge networks, exposure of lipid-binding sites, and collocation of amino-terminal helices at the cytoplasmic entrance. We also found that the hemichannel has a pore with a diameter of similar to 8 angstrom and selectively transports chloride ions. Our study provides structural insights into the permeant selectivity of Cx31.3 hemichannel.