开放型人钾通道的分子结构。
Molecular structure of an open human K channel.
机构信息
HHMI, The Rockefeller University, New York, NY 10065.
Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, New York, NY 10065.
出版信息
Proc Natl Acad Sci U S A. 2021 Nov 30;118(48). doi: 10.1073/pnas.2112267118.
K channels are metabolic sensors that translate intracellular ATP/ADP balance into membrane excitability. The molecular composition of K includes an inward-rectifier potassium channel (Kir) and an ABC transporter-like sulfonylurea receptor (SUR). Although structures of K have been determined in many conformations, in all cases, the pore in Kir is closed. Here, we describe human pancreatic K (hK) structures with an open pore at 3.1- to 4.0-Å resolution using single-particle cryo-electron microscopy (cryo-EM). Pore opening is associated with coordinated structural changes within the ATP-binding site and the channel gate in Kir. Conformational changes in SUR are also observed, resulting in an area reduction of contact surfaces between SUR and Kir. We also observe that pancreatic hK exhibits the unique (among inward-rectifier channels) property of PIP-independent opening, which appears to be correlated with a docked cytoplasmic domain in the absence of PIP.
K 通道是代谢传感器，可将细胞内 ATP/ADP 平衡转化为膜兴奋性。K 的分子组成包括内向整流钾通道 (Kir) 和 ABC 转运体样磺酰脲受体 (SUR)。尽管 K 的结构已在许多构象中确定，但在所有情况下，Kir 中的孔都是关闭的。在这里，我们使用单颗粒冷冻电镜 (cryo-EM) 在 3.1 到 4.0 Å 的分辨率下描述了具有开放孔的人胰腺 K (hK) 结构。孔的打开与 Kir 中的 ATP 结合位点和通道门内的协调结构变化相关。还观察到 SUR 的构象变化，导致 SUR 和 Kir 之间的接触表面面积减小。我们还观察到胰腺 hK 表现出独特的 (在内向整流通道中) 无 PIP 依赖性打开的特性，这似乎与 PIP 缺失时细胞质结构域的对接相关。
Zotero 插件