Bacterial Leucine Transporter

Specialized in small hydrophobic amino acids such as leucine and alanine, this transporter is powered by the gradient of sodium ions that is normally maintained by healthy cells across their membranes.

LeuT acts as a symporter, which means that it links the passage of a sodium ion across the cell membrane with the transport of the amino acid in the same direction.

It is a homologue of the proteins that remove chemical transmitters from the synapse and assist neurotransmission such as serotonin, dopamine, noradrenaline, glycine or GABA (-aminobutyric acid) transporters in neurons.

Leucine and alanine are the main amino acids that this protein brings across the membrane since it has a high affinity for these small hydrophobic molecules.

The concentration difference creates an electrochemical potential gradient that is used to catalyze the uptake of organic substrates (in this case leucine).

Two sets of alpha helices are thought to perform the rocking action by directly changing its shape after the binding of the amino acid to the structure.

[4] There is some evidence, however, that antidepressants may bind a bit deeper in the opening of human neurotransmitter transporters, due to their differences with LeuT; these are, a more packaged structure and extensions at the ends of the chain that allow them to interact with other proteins in the nerve cell.

[2] In line with this, as it can be seen in the image below, the sequence homology between the human sodium-dependent serotonin transporter (the target of SSRIs) and LeuT is only of 21.5%, though the tridimensional structure of both proteins shares a close resemblance.

Representation of LeuT. Polar residues are shown in blue and non polar in green. Image generated using VMD from PDB file 3F3E.
LeuT embedded in the membrane. Image generated using VMD from PDB file 3F3E.
2D-view of LeuT embedded in the membrane. Image generated using VMD from PDB file 3F3E.
Top-down view of LeuT with Citalopram bound to it. In the center of the protein there can be found the two sodium ions (labelled in blue) that are used to symport leucine through the transporter. This image was generated using Autodock from PDB file 3F3E.