Mechanism of sodium-coupling in sodium-coupled transporters

膜蛋白转运蛋白是使小分子如营养物质、离子、神经递质和毒素能够跨细胞膜转运的整合膜蛋白。它们在细胞生理学中起着核心作用，它们的失调可能导致疾病。相反，一些是潜在的药物靶点，另一些有助于将药物递送到细胞，或者它们的作用可能导致多药耐药性。转运蛋白可分为初级转运蛋白和次级转运蛋白。初级转运蛋白通过ATP的水解、氧化还原反应或光来提供能量，而次级转运蛋白利用储存在跨膜电化学梯度中的能量来进行转运过程。特别感兴趣的是二级转运蛋白中离子的共转运如何导致底物被携带穿过膜。事实上，这是一个主要的问题，所有二级运输（2）。例如，ASBTNM是胆汁酸转运蛋白ASBT和NTCP的细菌同源物，与两个钠离子共同转运其底物（1）。Mhp1是另一种正在实验室研究的蛋白质，它只运输一种。该项目将重点关注这些转运蛋白及其同系物，以研究钠离子结合的结构后果。

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 play a central role in cell physiology and their dysregulation can lead to disease. Conversely, some are potential drug targets and others aid in the delivery of drugs to cells or their action can cause multi-drug resistance. Transporters can be classified as primary or secondary transporters. Whereas primary transporters are energized by the hydrolysis of ATP, redox reactions or light, secondary transporters harness the energy stored in electrochemical gradients across the membrane to the transport process. Of particular interest is how the co-transport of ions in secondary transporters causes the substrate to be carried across the membrane. Indeed, this is a major question for all secondary transporters (2). For instance, ASBTNM, a bacterial homologue of the bile acid transporters ASBT and NTCP, co-transports its substrate with two sodium ions (1). Mhp1, another protein being investigated in the lab, transports only one. The project will focus on these transporters and their homologues to investigate the structural consequences of sodium-ion binding.