Introduction
Before you delve further into this blog one of the essential questions you should ask is: What is an NSS?
An NSS is a neurotransmitter sodium symporter in cell membranes. It allows the uptake of a neurotransmitter into the cell, removing it from the synapse and stopping the signalling. As we're sure you've noticed from the name, this action is coupled to sodium ion transport in the same direction allowing transport of neurotransmitter uphill. Examples of neurotransmitters removed are serotonin, dopamine, noradrenaline, glycine and GABA.
Even more importantly...What is LeuT?
LeuT is a bacterial homolog of NSSs which transports small hydrophobic amino acids in and out of bacterial cells, coupling this to sodium symport.
Why is LeuT significant in the scientific community right now?
LeuT is much easier to purify and crystallise than an NSS and so has been fundamental to obtain clues about its eukaryotic homologs, structurally, mechanistically and functionally. Two conformations of LeuT have been found previously:
- Substrate and ion bound occluded conformation
- Outward facing conformation (stabilised by competitive and non-competitive inhibitors).
Another important role LeuT has is to look at how therapeutic and illegal drugs form complexes with NSSs and so it has significant clinical relevance.
What is the focus of this article?
LeuT has enabled numerous breakthroughs with regard to NSSs however these have been limited because intermediate structures were not known. Now, two conformations have been crystallised, the outward open state and the inward open state and understanding of mechanisms has advanced.
