Mechanism of sodium-coupling in sodium-coupled transporters

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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.