The role of heme in ion channel function

金属元素铁参与各种生物系统是众所周知的。在许多情况下，铁以血红素基团的形式存在，最著名的是在血红蛋白中。血红素蛋白家族广泛，血红素在这些蛋白质中的参与是作为一个修复基团，其中的血红素与蛋白质结构密切相关。广泛的研究表明，血红素与特定蛋白质的结合决定了该分子的反应性。通过这种方式，通过将相同的血红素基团结合到不同的蛋白质结构中，可以实现大量的生物需求，如氧运输、各种底物的催化氧化、NO的合成、电子转移等。最近，越来越清楚的是，上面的描述只代表了血红素更复杂的生物学作用的一小部分，而对血红素的其他调节作用被忽视了。一个例子是离子通道功能的调节。离子通道蛋白形成一个孔，离子(如钾、钙、钠)可以通过这个孔穿过细胞膜。这些通道有打开和关闭的门，从而调节离子通过孔道的流动。这种离子流控制着许多重要的生物过程，如心脏跳动和大脑功能。越来越多的证据表明，血红素可以控制这些离子通道门的开启和关闭。通过与莱斯特大学建立的细胞生理学小组的合作，并结合计算和蛋白质组学方法，我们打算建立一个更详细的描述，说明血红素如何在许多不同的离子通道中发挥这些调节作用。

The involvement of the metallic element iron in various biological systems is well known. In many cases, iron is employed in the form of a heme group, most famously in hemoglobin. The family of heme proteins is vast, and the involvement of heme in these proteins is as a prosthetic group, in which the heme is tightly associated with the protein structure. Extensive studies have shown that the binding of heme to a particular protein defines the reactivity of that molecule. In this way a large number of biological requirements - such as oxygen transport, catalytic oxidation of all kinds of substrates, synthesis of NO, electron transfer etc - become accessible through incorporation of the same heme group into different protein structures. Very recently, it is becoming clear that the description above represents only a small part of a much more complex biological role for heme and that other, regulatory roles for heme have been overlooked. One example is in the regulation of ion channel function. Ion channel proteins form a pore through which ions (e.g. potassium, calcium, sodium) can travel through cell membranes. These channels have gates that open and close, and thus regulate the flow of ions through the pore. This ion flow governs many important biological processes such as beating of the heart and brain function. There is emerging evidence that heme can control opening and closing of these ion channel gates. Through a collaboration with the established cell physiology group at Leicester, and by incorporation of computational and proteomic approaches, we intend to build a more detailed description of how heme exerts these regulatory effects in a number of different ion channels.