Conformational states of membrane proteins: Technology development for bioscience

虽然生命需要水，但生命必须能够控制水的流动。例如，如果一个人(70%的水)跳进游泳池，他们不会像方糖一样溶解。这是因为我们在游泳池水和牢房里的水之间有一道屏障。这种屏障是膜或脂双层，它是由油性化合物组成的。双层是必不可少的，它把重要的东西挡在里面，把有毒的东西挡在外面。所有的有机体都有这些双层。在它们自己的双层上会简单地阻止所有的运输，因此我们不能吸收营养，也不能清除废物。因此，嵌入在膜中的蛋白质需要充当闸门守护者，以控制离子、营养物质、废物和蛋白质在脂质双层中的移动。这些蛋白质也是一个细胞和另一个细胞之间的电话连接。人类的神经冲动从神经元传递一种递质(小化学物质)的触发释放。递质通过促进细胞中的一些变化与另一个细胞相互作用，每个细胞都使用膜蛋白作为这一过程的一部分。控制离子通过双层的膜蛋白称为离子通道。它们必须像水龙头一样，能够完全关闭以阻止泄漏，但在需要时也必须打开。许多疾病是由膜蛋白不能正常工作引起的。如果我们要治疗这些疾病，我们需要了解膜蛋白是如何工作的。蛋白质结晶学改变了我们对蛋白质的理解。它使我们能够看到结构中的每个原子，并对蛋白质的功能有很大的了解。这种科学方法导致了许多新药的开发。然而，这项技术一次只能看到蛋白质的一种状态。我们建议开发一种新的方法，使我们能够详细地了解膜蛋白如何在开放和关闭状态之间移动。我们选择研究人类的疼痛受体和细菌的渗透应激生存蛋白。这些都是重要的系统，具有明显的医疗益处，治疗疼痛和设计新的抗生素。

Although life requires water, life must be able to control the flow of water. As an example, if a person (70% water) jumps into a swimming pool they do not dissolve like a sugar cube. This is because we have a barrier between the swimming pool water and the water inside our cells. This barrier is the membrane or lipid bilayer, it is made of oily compounds. The bilayer is essential it keeps important things in and poisonous things out. All organisms have these bilayers. On their own bilayers would simply block all transport, thus we could not take up nutrients nor could we get rid of waste. Proteins embedded in this membrane are thus needed to act as gate keepers to control movements of ions, nutrients, waste and proteins across the lipid bilayer. These proteins are also the telephone connections between one cell and another. The nerve impulse in humans transmits trigger release of a transmitter (small chemical) from the neuron. The transmitter interacts with another cell by promoting some change in the cell, each cell uses membrane proteins as part of this process. Membrane proteins that control ions movement across the bilayer are called ion channels. They must, like a tap, be able to fully closed to stop leaks but they must also open when required. Many diseases are caused by membrane proteins not working properly. If we are to treat these diseases we need to understand how membrane proteins work. Protein crystallography has transformed our understanding of proteins. It allows us to see every atom in the structure and understand a great deal about the function of the protein. This scientific approach has led to the development of many new drugs. However, this technique can only see one state of the protein at a time. We propose to develop a new approach that will allow us to see in detail exactly how membrane proteins move between the open and closed states. We have chosen to study the pain receptors in humans and the osmotic stress survival proteins in bacteria. These are important systems with obvious medical benefits, treatment of pain and design of new antibiotics.