Mechanism of sodium-coupling in sodium-coupled transporters

膜蛋白转运蛋白是一种完整的膜蛋白，它能使小分子如营养物质、离子、神经递质和毒素等跨细胞膜运输。它们通过交替打开和关闭膜的一侧或另一侧的结合位置来实现这一点。他们可以分为两大类。初级转运蛋白使用ATP等能源，而二级转运蛋白使用离子梯度来促进运输。Mhp1是一种二级转运蛋白，它利用钠离子梯度来驱动分子(底物)进入细胞。它是一个蛋白质超家族的成员，该家族还包括人类神经递质蛋白质。这是这个超家族中第一个以多种构象被解决的蛋白质，显示了蛋白质结构是如何改变的，从而使其能够通过膜运输分子。以前的研究已经显示了钠离子和底物如何与蛋白质结合，并揭示了伴随结合的构象变化。这个项目的目的是了解这一家族转运蛋白中这些分子的结合和释放如何驱动构象变化，以及钠离子的结合如何与底物的结合相结合。

Membrane protein transporters are integral membrane proteins that enable small molecules such as nutrients, ions, neurotransmitters, and toxins to be transported across cellular membranes. They do this by alternately opening and closing the binding sites to one side or the other of the membranes. They can be divided into two major groups. Primary transporters use energy sources such as ATP whereas secondary transporters use ion gradients to facilitate transport. Mhp1 is a secondary transporter that harnesses the sodium ion gradient to drive the uptake of molecules (substrates) into the cell. It is a member of a large superfamily of proteins that also include human neurotransmitter proteins. It was the first protein in this superfamily to be solved in multiple conformations showing how the protein structure changes to allow it to transport molecules across the membrane. Previous studies have shown how the sodium ion and substrate bind to the protein and revealed the conformational changes that accompany binding. The object of this project is to understand how binding and release of these molecules in this family of transporters drives the conformational changes and how the binding of the sodium ion is coupled with the binding of the substrate.