Single-particle cryo-EM structure of a voltage-activated potassium channel in lipid nanodiscs.
Single-particle cryo-EM structure of a voltage-activated potassium channel in lipid nanodiscs.
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DOI：
10.7554/elife.37558
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发表时间：
2018-08-15
期刊：
影响因子：
7.7
通讯作者：
Swartz KJ
中科院分区：
文献类型：
--
作者：
Matthies D;Bae C;Toombes GE;Fox T;Bartesaghi A;Subramaniam S;Swartz KJ
电压激活的钾（Kv）通道响应于膜去极化而打开以传导K+离子，随后通过不同的失活机制进入非传导状态。洗涤剂溶解的KV通道的X射线结构似乎已经捕获了开放状态，即使在没有跨膜电压的情况下，非导电C型失活状态将在膜中占主导地位。然而，在脂质双层环境中的电压激活的离子通道的结构尚未报道。在这里，我们报告的Kv1.2-2.1桨嵌合体通道重组成脂质纳米盘使用单粒子冷冻电子显微镜的结构。在胞质结构域的分辨率约为3 Å，跨膜结构域的分辨率约为4 Å的情况下，纳米盘中确定的结构与之前确定的X射线结构相似。我们的研究结果表明，洗涤剂和脂质双层环境之间的结构差异很大是不可能的，并使我们能够提出可能的C型失活的结构机制。
Voltage-activated potassium (Kv) channels open to conduct K+ ions in response to membrane depolarization, and subsequently enter non-conducting states through distinct mechanisms of inactivation. X-ray structures of detergent-solubilized Kv channels appear to have captured an open state even though a non-conducting C-type inactivated state would predominate in membranes in the absence of a transmembrane voltage. However, structures for a voltage-activated ion channel in a lipid bilayer environment have not yet been reported. Here we report the structure of the Kv1.2–2.1 paddle chimera channel reconstituted into lipid nanodiscs using single-particle cryo-electron microscopy. At a resolution of ~3 Å for the cytosolic domain and ~4 Å for the transmembrane domain, the structure determined in nanodiscs is similar to the previously determined X-ray structure. Our findings show that large differences in structure between detergent and lipid bilayer environments are unlikely, and enable us to propose possible structural mechanisms for C-type inactivation.