一个血红素结合结构域控制着ATP依赖性钾通道的调节。
A heme-binding domain controls regulation of ATP-dependent potassium channels.
作者信息
Burton Mark J, Kapetanaki Sofia M, Chernova Tatyana, Jamieson Andrew G, Dorlet Pierre, Santolini Jérôme, Moody Peter C E, Mitcheson John S, Davies Noel W, Schmid Ralf, Raven Emma L, Storey Nina M
机构信息
Department of Molecular and Cell Biology, University of Leicester, Leicester LE1 9HN, United Kingdom;
Department of Chemistry, University of Leicester, Leicester LE1 7RH, United Kingdom;
出版信息
Proc Natl Acad Sci U S A. 2016 Apr 5;113(14):3785-90. doi: 10.1073/pnas.1600211113. Epub 2016 Mar 22.
Heme iron has many and varied roles in biology. Most commonly it binds as a prosthetic group to proteins, and it has been widely supposed and amply demonstrated that subtle variations in the protein structure around the heme, including the heme ligands, are used to control the reactivity of the metal ion. However, the role of heme in biology now appears to also include a regulatory responsibility in the cell; this includes regulation of ion channel function. In this work, we show that cardiac KATP channels are regulated by heme. We identify a cytoplasmic heme-binding CXXHX16H motif on the sulphonylurea receptor subunit of the channel, and mutagenesis together with quantitative and spectroscopic analyses of heme-binding and single channel experiments identified Cys628 and His648 as important for heme binding. We discuss the wider implications of these findings and we use the information to present hypotheses for mechanisms of heme-dependent regulation across other ion channels.
血红素铁在生物学中具有多种不同的作用。最常见的是它作为辅基与蛋白质结合，并且人们普遍认为且有充分证据表明，血红素周围蛋白质结构的细微变化，包括血红素配体，可用于控制金属离子的反应性。然而，血红素在生物学中的作用现在似乎还包括在细胞中的调节职责；这包括对离子通道功能的调节。在这项工作中，我们表明心脏KATP通道受血红素调节。我们在该通道的磺脲类受体亚基上鉴定出一个胞质血红素结合CXXHX16H基序，通过诱变以及对血红素结合的定量和光谱分析以及单通道实验，确定Cys628和His648对血红素结合很重要。我们讨论了这些发现的更广泛意义，并利用这些信息提出了关于其他离子通道血红素依赖性调节机制的假设。
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