Mechanism of sodium-coupling in sodium-coupled transporters

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.