Control of KirBac3.1 potassium channel gating at the interface between cytoplasmic domains.
Control of KirBac3.1 potassium channel gating at the interface between cytoplasmic domains.
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DOI：
10.1074/jbc.m113.501833
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发表时间：
2014-01-03
期刊：
影响因子：
--
通讯作者：
Tucker SJ
中科院分区：
文献类型：
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作者：
Zubcevic L;Bavro VN;Muniz JR;Schmidt MR;Wang S;De Zorzi R;Venien-Bryan C;Sansom MS;Nichols CG;Tucker SJ
背景：KirBac3.1 是真核 Kir 通道的原核同源物。结果：突变通道的高分辨率晶体结构揭示了一种新颖的开放构象。结论：细胞质结构域之间的亚基间界面控制通道门控。意义：这些发现有助于定义对原核和真核 Kir 通道门控重要的结构。 KirBac 通道是哺乳动物内向整流钾 (Kir) 通道的原核同源物，KirBac3.1 的最新结构为了解 Kir 通道门控的结构基础提供了重要的见解。在这项研究中，我们证明 KirBac3.1 通道活性具有很强的 pH 依赖性，并且我们使用 X 射线晶体学来确定位于细胞质结构域 (CTD) 中的激活突变 (S205L) 引起的结构变化。这种突变稳定了一种新的能量有利的开放构象，其中 CTD 中亚基间界面的变化也改变了内部细胞质腔的静电势。这些结果为该突变的激活作用提供了结构解释，并提供了对 CTD 在 Kir 通道门控中的作用的更深入的了解。
Background: KirBac3.1 is a prokaryotic homolog of eukaryotic Kir channels. Results: A high-resolution crystal structure of a mutant channel reveals a novel open conformation. Conclusion: The intersubunit interface between the cytoplasmic domains controls channel gating. Significance: These findings help define the structures important for gating in prokaryotic and eukaryotic Kir channels. KirBac channels are prokaryotic homologs of mammalian inwardly rectifying potassium (Kir) channels, and recent structures of KirBac3.1 have provided important insights into the structural basis of gating in Kir channels. In this study, we demonstrate that KirBac3.1 channel activity is strongly pH-dependent, and we used x-ray crystallography to determine the structural changes that arise from an activatory mutation (S205L) located in the cytoplasmic domain (CTD). This mutation stabilizes a novel energetically favorable open conformation in which changes at the intersubunit interface in the CTD also alter the electrostatic potential of the inner cytoplasmic cavity. These results provide a structural explanation for the activatory effect of this mutation and provide a greater insight into the role of the CTD in Kir channel gating.